[{"volume":4,"publication_identifier":{"eissn":["2835-8279"]},"has_accepted_license":"1","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"21282","publication":"PRX Life","ddc":["570"],"status":"public","corr_author":"1","oa_version":"Published Version","department":[{"_id":"GaTk"}],"intvolume":"         4","file_date_updated":"2026-02-24T06:57:44Z","project":[{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos"}],"date_created":"2026-02-17T08:29:10Z","author":[{"first_name":"David","full_name":"Brückner, David","last_name":"Brückner","orcid":"0000-0001-7205-2975","id":"e1e86031-6537-11eb-953a-f7ab92be508d"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","full_name":"Tkačik, Gašper","first_name":"Gašper"}],"quality_controlled":"1","acknowledgement":"We thank Edouard Hannezo, Anna Kicheva, Fridtjof Brauns, and all members of the Brückner and Tkačik groups for feedback and inspiring discussions. This work was supported in part by European Research Council ERC-2023-SyG “Dynatrans” Grant No. 101118866 (G.T.). This work was conducted while visiting the Okinawa Institute of Science and Technology (OIST) through the Theoretical Sciences Visiting Program (TSVP); at the Kavli Institute for Theoretical Physics (KITP) Santa Barbara, supported by NSF Grant No. PHY-1748958 and the Gordon and Betty Moore Foundation Grant No. 2919.02; and at Lucullus, Vienna.","OA_place":"publisher","oa":1,"publisher":"American Physical Society","arxiv":1,"external_id":{"arxiv":["2510.24536"]},"PlanS_conform":"1","title":"Marr's three levels for embryonic development: Information, dynamical systems, gene networks","publication_status":"published","year":"2026","abstract":[{"text":"Developmental patterning comprises processes that range from purely instructed, where external signals specify cell fates, to fully self-organized, where spatial patterns emerge autonomously through cellular interactions. We propose that both extremes—as well as the continuum of intermediate cases—can be conceptualized as information-processing systems, whose operation can be described using “Marr's three levels of analysis”: the computational problem being solved, the algorithms employed, and their molecular implementation. At the first level, we argue that normative theories, such as information-theoretic optimization principles, provide a formalization of the computational problem. At the second level, we show how simplified information-processing architectures provide a framework for developmental algorithms, which are formalized mathematically using dynamical systems theory. At the third level, the implementation of developmental algorithms is described by mechanistic biophysical and gene regulatory network models.","lang":"eng"}],"OA_type":"gold","article_processing_charge":"Yes","article_type":"original","doi":"10.1103/fdcf-dkws","DOAJ_listed":"1","date_updated":"2026-02-24T07:00:16Z","file":[{"access_level":"open_access","checksum":"99ef02dd741c4536eeefd12d409d5269","date_created":"2026-02-24T06:57:44Z","creator":"dernst","file_size":1147994,"date_updated":"2026-02-24T06:57:44Z","file_id":"21352","relation":"main_file","content_type":"application/pdf","success":1,"file_name":"2026_PRXLife_Brueckner.pdf"}],"date_published":"2026-01-23T00:00:00Z","month":"01","language":[{"iso":"eng"}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"article_number":"017001","citation":{"apa":"Brückner, D., &#38; Tkačik, G. (2026). Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. <i>PRX Life</i>. American Physical Society. <a href=\"https://doi.org/10.1103/fdcf-dkws\">https://doi.org/10.1103/fdcf-dkws</a>","short":"D. Brückner, G. Tkačik, PRX Life 4 (2026).","ieee":"D. Brückner and G. Tkačik, “Marr’s three levels for embryonic development: Information, dynamical systems, gene networks,” <i>PRX Life</i>, vol. 4. American Physical Society, 2026.","chicago":"Brückner, David, and Gašper Tkačik. “Marr’s Three Levels for Embryonic Development: Information, Dynamical Systems, Gene Networks.” <i>PRX Life</i>. American Physical Society, 2026. <a href=\"https://doi.org/10.1103/fdcf-dkws\">https://doi.org/10.1103/fdcf-dkws</a>.","ista":"Brückner D, Tkačik G. 2026. Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. PRX Life. 4, 017001.","mla":"Brückner, David, and Gašper Tkačik. “Marr’s Three Levels for Embryonic Development: Information, Dynamical Systems, Gene Networks.” <i>PRX Life</i>, vol. 4, 017001, American Physical Society, 2026, doi:<a href=\"https://doi.org/10.1103/fdcf-dkws\">10.1103/fdcf-dkws</a>.","ama":"Brückner D, Tkačik G. Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. <i>PRX Life</i>. 2026;4. doi:<a href=\"https://doi.org/10.1103/fdcf-dkws\">10.1103/fdcf-dkws</a>"},"day":"23"},{"date_updated":"2026-07-16T09:58:04Z","month":"07","researchdata_availability":"no","date_published":"2026-07-15T00:00:00Z","file":[{"file_size":2550345,"creator":"dernst","date_updated":"2026-07-16T09:54:55Z","date_created":"2026-07-16T09:54:55Z","checksum":"28861d31d0f6cf541aaca04faaed1767","success":1,"content_type":"application/pdf","file_id":"22352","relation":"main_file","access_level":"open_access","file_name":"2026_PhysicalReviewLetters_Zhang.pdf"}],"language":[{"iso":"eng"}],"day":"15","citation":{"apa":"Zhang, C. Y., Mateu Hoyos, P., Brückner, D., &#38; Tkačik, G. (2026). Nonlocal decoding of positional and correlational information during development. <i>Physical Review Letters</i>. American Physical Society. <a href=\"https://doi.org/10.1103/mbjk-v4ym\">https://doi.org/10.1103/mbjk-v4ym</a>","short":"C.Y. Zhang, P. Mateu Hoyos, D. Brückner, G. Tkačik, Physical Review Letters 137 (2026).","chicago":"Zhang, Chen Y, Pablo Mateu Hoyos, David Brückner, and Gašper Tkačik. “Nonlocal Decoding of Positional and Correlational Information during Development.” <i>Physical Review Letters</i>. American Physical Society, 2026. <a href=\"https://doi.org/10.1103/mbjk-v4ym\">https://doi.org/10.1103/mbjk-v4ym</a>.","ieee":"C. Y. Zhang, P. Mateu Hoyos, D. Brückner, and G. Tkačik, “Nonlocal decoding of positional and correlational information during development,” <i>Physical Review Letters</i>, vol. 137. American Physical Society, 2026.","ista":"Zhang CY, Mateu Hoyos P, Brückner D, Tkačik G. 2026. Nonlocal decoding of positional and correlational information during development. Physical Review Letters. 137, 038401.","mla":"Zhang, Chen Y., et al. “Nonlocal Decoding of Positional and Correlational Information during Development.” <i>Physical Review Letters</i>, vol. 137, 038401, American Physical Society, 2026, doi:<a href=\"https://doi.org/10.1103/mbjk-v4ym\">10.1103/mbjk-v4ym</a>.","ama":"Zhang CY, Mateu Hoyos P, Brückner D, Tkačik G. Nonlocal decoding of positional and correlational information during development. <i>Physical Review Letters</i>. 2026;137. doi:<a href=\"https://doi.org/10.1103/mbjk-v4ym\">10.1103/mbjk-v4ym</a>"},"article_number":"038401","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"lang":"eng","text":"In many developmental systems, cells differentiate into a tissue by reading out morphogen concentration fields, a process fundamentally limited by noise. How much can the precision of this process be improved by nonlocal information, e.g., via cell-cell communication? Using a Bayes-optimal framework, we show that positional inference depends crucially on morphogen spatial correlations and on the \"structural prior\" that encodes the geometry of the cellular lattice performing the readout, thereby determining what a cell can reliably assume about the position of its neighbors when interpreting nonlocal morphogen signals. We derive upper bounds on positional information gain due to nonlocal readout and identify signal processing algorithms that approximate optimal positional inference, as well as simple chemical reaction schemes which implement such algorithms. Our theory suggests that correlational information can be exploited to significantly enhance developmental precision."}],"year":"2026","publication_status":"published","OA_type":"hybrid","article_processing_charge":"Yes (via OA deal)","dataavailabilitystatement":"Code to evaluate PI, to run algorithmic implementations of ALP and RLP decoding, and to\r\nperform simulations is publicly available at https://github.com/alex-chenyi-zhang/nonlocdec_pici.","doi":"10.1103/mbjk-v4ym","article_type":"original","date_created":"2026-07-14T05:38:28Z","project":[{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","grant_number":"101118866"}],"oa":1,"OA_place":"publisher","das_tickbox":"1","author":[{"id":"81b43fb8-c9d5-11ef-bf68-ade532a1f204","full_name":"Zhang, Chen Y","last_name":"Zhang","first_name":"Chen Y"},{"id":"50b236c7-50c1-11ef-bb9a-a2375694f8b5","last_name":"Mateu Hoyos","full_name":"Mateu Hoyos, Pablo","first_name":"Pablo"},{"id":"e1e86031-6537-11eb-953a-f7ab92be508d","orcid":"0000-0001-7205-2975","first_name":"David","last_name":"Brückner","full_name":"Brückner, David"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","full_name":"Tkačik, Gašper","first_name":"Gašper"}],"quality_controlled":"1","acknowledgement":"This work was supported in part\r\nby European Research Council No. ERC-2023-SyG\r\n“DynaTrans” Grant No. 101118866 (G. T.). We thank\r\nPieter Rein ten Wolde and Vahe Galstyan for stimulating\r\ndiscussions.","publisher":"American Physical Society","title":"Nonlocal decoding of positional and correlational information during development","PlanS_conform":"1","type":"journal_article","has_accepted_license":"1","publication_identifier":{"eissn":[" 1079-7114"],"issn":["0031-9007"]},"supplementarymaterial":"no","volume":137,"publication":"Physical Review Letters","_id":"22326","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","status":"public","corr_author":"1","ddc":["530"],"scopus_import":"1","file_date_updated":"2026-07-16T09:54:55Z","intvolume":"       137","department":[{"_id":"GaTk"},{"_id":"EdHa"},{"_id":"GradSch"}]},{"intvolume":"       123","department":[{"_id":"GaTk"}],"file_date_updated":"2026-07-20T13:12:47Z","scopus_import":"1","oa_version":"Published Version","corr_author":"1","related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-art-of-proper-flickering/","description":"News on ISTA website","relation":"press_release"}]},"ddc":["570"],"status":"public","_id":"22363","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication":"Proceedings of the National Academy of Sciences of the United States of America","supplementarymaterial":"yes","volume":123,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"type":"journal_article","has_accepted_license":"1","external_id":{"pmid":["42406962"]},"title":"Invariant nonequilibrium dynamics in gene regulation optimize information flow","issue":"28","publisher":"National Academy of Sciences","OA_place":"publisher","das_tickbox":"1","author":[{"first_name":"Benjamin","full_name":"Zoller, Benjamin","last_name":"Zoller"},{"full_name":"Benichou, Alexis","last_name":"Benichou","first_name":"Alexis","id":"3a67230c-5fc0-11ef-a673-de9a2ffadafe"},{"first_name":"Thomas","last_name":"Gregor","full_name":"Gregor, Thomas"},{"last_name":"Tkačik","full_name":"Tkačik, Gašper","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"acknowledgement":"This work was supported by the French NationalResearch Agency (ANR-20-CE12-0028 “ChroDynE” and ANR-23-CE13-0021“GastruCyp” and ANR-10 LABX-73 “Revive;” all T.G.), and by funding from theEuropean Research Council (ERC-2023-SyG, “Dynatrans,” 101118866, T.G. andG.T.). This work was also supported in part by the U.S. NSF, through the Centerfor the Physics of Biological Function (PHY-1734030, T.G.), and by NIH GrantsR01GM097275, U01DA047730, and U01DK127429 (T.G.)","quality_controlled":"1","oa":1,"pmid":1,"project":[{"grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9"}],"date_created":"2026-07-19T22:01:46Z","doi":"10.1073/pnas.2524855123","article_type":"original","OA_type":"hybrid","dataavailabilitystatement":"Software code data have been deposited in Institute Pasteur GitHub (https://gitlab.pasteur.fr/tglab/invariantpromoterdynamicspaper) (51).","article_processing_charge":"Yes","publication_status":"published","abstract":[{"lang":"eng","text":"Eukaryotic gene regulation relies on stochastic yet controlled promoter switching, in which genes transition between transcriptionally active and inactive states. Despite the molecular complexity of this process, recent studies have revealed a surprising invariance of the “switching correlation time” (TC)—the characteristic decay time of the autocorrelation function of promoter activity fluctuations—across gene expression levels in multiple genes and organisms. A biophysically plausible explanation for this invariance has so far been lacking. Here, we show that this empirical constraint imposes stringent requirements on minimal yet realistic models of transcriptional regulation. Specifically, reproducing TC–invariance requires regulatory architectures with at least four internal states and nonequilibrium dynamics that break detailed balance. Using Bayesian inference on Drosophila gap gene expression data, we demonstrate that such models i) quantitatively reproduce the observed TC–invariance, ii) remain robust to parameter perturbations, and iii) maximize information transmission from transcription factor concentration to gene expression. Remarkably, the TC-invariant modulation strategy we identify as optimal closely parallels contemporary control-theoretic results on the modulation of stochastic switching systems. Taken together, our results suggest that eukaryotic transcriptional regulation operates in a nonequilibrium regime to balance precision, reaction-rate limitations, and energy dissipation, thereby achieving near-optimal information transmission under fundamental physical constraints."}],"year":"2026","article_number":"e2524855123","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"day":"14","citation":{"ieee":"B. Zoller, A. Benichou, T. Gregor, and G. Tkačik, “Invariant nonequilibrium dynamics in gene regulation optimize information flow,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 123, no. 28. National Academy of Sciences, 2026.","chicago":"Zoller, Benjamin, Alexis Benichou, Thomas Gregor, and Gašper Tkačik. “Invariant Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2026. <a href=\"https://doi.org/10.1073/pnas.2524855123\">https://doi.org/10.1073/pnas.2524855123</a>.","ista":"Zoller B, Benichou A, Gregor T, Tkačik G. 2026. Invariant nonequilibrium dynamics in gene regulation optimize information flow. Proceedings of the National Academy of Sciences of the United States of America. 123(28), e2524855123.","mla":"Zoller, Benjamin, et al. “Invariant Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 123, no. 28, e2524855123, National Academy of Sciences, 2026, doi:<a href=\"https://doi.org/10.1073/pnas.2524855123\">10.1073/pnas.2524855123</a>.","ama":"Zoller B, Benichou A, Gregor T, Tkačik G. Invariant nonequilibrium dynamics in gene regulation optimize information flow. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2026;123(28). doi:<a href=\"https://doi.org/10.1073/pnas.2524855123\">10.1073/pnas.2524855123</a>","apa":"Zoller, B., Benichou, A., Gregor, T., &#38; Tkačik, G. (2026). Invariant nonequilibrium dynamics in gene regulation optimize information flow. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2524855123\">https://doi.org/10.1073/pnas.2524855123</a>","short":"B. Zoller, A. Benichou, T. Gregor, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 123 (2026)."},"language":[{"iso":"eng"}],"file":[{"access_level":"open_access","checksum":"f4d82dd706ff1629db68d71190288350","date_created":"2026-07-20T13:12:47Z","creator":"dernst","file_size":24580098,"date_updated":"2026-07-20T13:12:47Z","relation":"main_file","file_id":"22376","content_type":"application/pdf","success":1,"file_name":"2026_PNAS_Zoller.pdf"}],"month":"07","researchdata_availability":"yes","date_published":"2026-07-14T00:00:00Z","date_updated":"2026-08-04T09:21:10Z"},{"status":"public","ddc":["570"],"corr_author":"1","oa_version":"Published Version","scopus_import":"1","file_date_updated":"2025-01-20T10:10:04Z","isi":1,"department":[{"_id":"GaTk"}],"intvolume":"       122","has_accepted_license":"1","type":"journal_article","volume":122,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"publication":"Proceedings of the National Academy of Sciences","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"18849","publisher":"National Academy of Sciences","issue":"1","title":"Deriving a genetic regulatory network from an optimization principle","external_id":{"pmid":["39752518"],"isi":["001392772400001"]},"date_created":"2025-01-19T23:01:50Z","project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","call_identifier":"FWF"},{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos"},{"grant_number":"RGP0034/2018","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","_id":"2665AAFE-B435-11E9-9278-68D0E5697425"}],"pmid":1,"oa":1,"author":[{"id":"3E999752-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1287-3779","first_name":"Thomas R","full_name":"Sokolowski, Thomas R","last_name":"Sokolowski"},{"first_name":"Thomas","full_name":"Gregor, Thomas","last_name":"Gregor"},{"first_name":"William","full_name":"Bialek, William","last_name":"Bialek"},{"first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","acknowledgement":"We thank Nicholas H. Barton for his comments on the manuscript, Benjamin Zoller for helpful discussions, and Aleksandra Walczak and Curtis Callan for early collaborations that shaped this work. Special thanks to Eric F. Wieschaus for many persistently inspiring conversations. This work was supported in part by the Human Frontiers Science Program; the Austrian Science Fund (FWF P28844); by the European Research Council grant DynaTrans (101118866); by U.S. NSF, through the Center for the Physics of Biological Function (PHY–1734030); by NIH Grants R01GM097275, U01DA047730, and U01DK127429; by the John Simon Guggenheim Memorial Foundation; and by the LOEWE priority program “Center for Multiscale Modeling in Life Sciences” (CMMS), sponsored by the Hessian Ministry for Science and Research, Arts and Culture (HMWK).","OA_place":"publisher","article_type":"original","doi":"10.1073/pnas.2402925121","year":"2025","abstract":[{"text":"Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the Drosophila embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks.","lang":"eng"}],"publication_status":"published","OA_type":"hybrid","article_processing_charge":"Yes (in subscription journal)","language":[{"iso":"eng"}],"citation":{"ama":"Sokolowski TR, Gregor T, Bialek W, Tkačik G. Deriving a genetic regulatory network from an optimization principle. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(1). doi:<a href=\"https://doi.org/10.1073/pnas.2402925121\">10.1073/pnas.2402925121</a>","mla":"Sokolowski, Thomas R., et al. “Deriving a Genetic Regulatory Network from an Optimization Principle.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1, e2402925121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2402925121\">10.1073/pnas.2402925121</a>.","ista":"Sokolowski TR, Gregor T, Bialek W, Tkačik G. 2025. Deriving a genetic regulatory network from an optimization principle. Proceedings of the National Academy of Sciences. 122(1), e2402925121.","ieee":"T. R. Sokolowski, T. Gregor, W. Bialek, and G. Tkačik, “Deriving a genetic regulatory network from an optimization principle,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1. National Academy of Sciences, 2025.","chicago":"Sokolowski, Thomas R, Thomas Gregor, William Bialek, and Gašper Tkačik. “Deriving a Genetic Regulatory Network from an Optimization Principle.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2402925121\">https://doi.org/10.1073/pnas.2402925121</a>.","short":"T.R. Sokolowski, T. Gregor, W. Bialek, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Sokolowski, T. R., Gregor, T., Bialek, W., &#38; Tkačik, G. (2025). Deriving a genetic regulatory network from an optimization principle. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2402925121\">https://doi.org/10.1073/pnas.2402925121</a>"},"day":"07","article_number":"e2402925121","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"date_updated":"2026-02-16T12:26:51Z","date_published":"2025-01-07T00:00:00Z","month":"01","file":[{"file_id":"18862","relation":"main_file","success":1,"content_type":"application/pdf","checksum":"8dbfc7d495413340225ebfae69b0cf9a","date_created":"2025-01-20T10:10:04Z","date_updated":"2025-01-20T10:10:04Z","creator":"dernst","file_size":19073585,"access_level":"open_access","file_name":"2025_PNAS_Sokolowski.pdf"}]},{"date_updated":"2026-05-06T12:43:59Z","date_published":"2025-01-07T00:00:00Z","month":"01","file":[{"access_level":"open_access","creator":"dernst","date_updated":"2025-01-20T09:38:32Z","file_size":30943709,"date_created":"2025-01-20T09:38:32Z","checksum":"86a8d25a6e282aeb4128f1d0b86ff911","success":1,"content_type":"application/pdf","relation":"main_file","file_id":"18859","file_name":"2025_PNAS_Perkins.pdf"}],"language":[{"iso":"eng"}],"citation":{"short":"M.L. Perkins, J. Crocker, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025).","apa":"Perkins, M. L., Crocker, J., &#38; Tkačik, G. (2025). Chromatin enables precise and scalable gene regulation with factors of limited specificity. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2411887121\">https://doi.org/10.1073/pnas.2411887121</a>","ama":"Perkins ML, Crocker J, Tkačik G. Chromatin enables precise and scalable gene regulation with factors of limited specificity. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(1). doi:<a href=\"https://doi.org/10.1073/pnas.2411887121\">10.1073/pnas.2411887121</a>","mla":"Perkins, Mindy Liu, et al. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1, e2411887121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2411887121\">10.1073/pnas.2411887121</a>.","ista":"Perkins ML, Crocker J, Tkačik G. 2025. Chromatin enables precise and scalable gene regulation with factors of limited specificity. Proceedings of the National Academy of Sciences. 122(1), e2411887121.","chicago":"Perkins, Mindy Liu, Justin Crocker, and Gašper Tkačik. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2411887121\">https://doi.org/10.1073/pnas.2411887121</a>.","ieee":"M. L. Perkins, J. Crocker, and G. Tkačik, “Chromatin enables precise and scalable gene regulation with factors of limited specificity,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1. National Academy of Sciences, 2025."},"day":"07","article_number":"e2411887121","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"year":"2025","abstract":[{"lang":"eng","text":"Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs). Under what conditions and by how much can chromatin reduce regulatory errors on a global scale? We use a theoretical approach to compare two scenarios for gene regulation: one that relies on TF binding to free DNA alone and one that uses a combination of TFs and chromatin-regulating PFs to achieve desired gene expression patterns. We find, first, that chromatin effectively silences groups of genes that should be simultaneously OFF, thereby allowing more accurate graded control of expression for the remaining ON genes. Second, chromatin buffers the deleterious consequences of nontarget binding as the number of OFF genes grows, permitting a substantial expansion in regulatory complexity. Third, chromatin-based regulation productively co-opts nontarget TF binding for ON genes in order to establish a “leaky” baseline expression level, which targeted activator or repressor binding subsequently up- or down-modulates. Thus, on a global scale, using chromatin simultaneously alleviates pressure for high specificity of regulatory interactions and enables an increase in genome size with minimal impact on global expression error."}],"publication_status":"published","article_processing_charge":"No","OA_type":"hybrid","article_type":"original","doi":"10.1073/pnas.2411887121","APC_amount":"3261,23 EUR","date_created":"2025-01-19T23:01:51Z","project":[{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos"}],"pmid":1,"oa":1,"acknowledgement":"M.L.P. was supported by the European Molecular Biology Laboratory (EMBL) Interdisciplinary Postdoc Programme (EIPOD4 fellowships), cofunded by Marie SkÅ‚odowska-Curie Actions (Grant Agreement No. 847543). J.C. and M.L.P. were supported by EMBL Core Funding and Theory@EMBL. This work is supported by European Research Council Grant DynaTrans (101118866) to G.T. We would like to thank the members of the J.C. and G.T. groups, especially Natalia Misunou, Michal Hledík, and Réka Borbély, for helpful feedback and discussion. We also thank EMBL IT Services for the use of high performance computing resources.","author":[{"first_name":"Mindy Liu","last_name":"Perkins","full_name":"Perkins, Mindy Liu"},{"last_name":"Crocker","full_name":"Crocker, Justin","first_name":"Justin"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik","first_name":"Gašper"}],"quality_controlled":"1","OA_place":"publisher","publisher":"National Academy of Sciences","issue":"1","title":"Chromatin enables precise and scalable gene regulation with factors of limited specificity","external_id":{"isi":["001392765300001"],"pmid":["39793086"]},"has_accepted_license":"1","type":"journal_article","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"volume":122,"publication":"Proceedings of the National Academy of Sciences","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"18850","related_material":{"link":[{"relation":"software","url":"https://github.com/officerredshirt/network_crosstalk"}]},"ddc":["570"],"corr_author":"1","status":"public","oa_version":"Published Version","scopus_import":"1","file_date_updated":"2025-01-20T09:38:32Z","isi":1,"department":[{"_id":"GaTk"}],"intvolume":"       122"},{"publication":"Annual Review of Biophysics","_id":"19701","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","has_accepted_license":"1","page":"249-274","publication_identifier":{"eissn":["1936-1238"]},"volume":54,"isi":1,"file_date_updated":"2025-05-19T07:55:51Z","intvolume":"        54","department":[{"_id":"GaTk"}],"oa_version":"Published Version","status":"public","corr_author":"1","ddc":["570"],"scopus_import":"1","oa":1,"pmid":1,"OA_place":"publisher","acknowledgement":"G.T. acknowledges the support of the Human Frontiers Science Program (HFSP), the Austrian Science Fund (FWF 10.55776/P34015, 10.55776/P28844), and the European Research Council Synergy DYNATRANS (ERC-2023-SyG 101118866) grant. P.R.t.W. performed his work at the research institute AMOLF and acknowledges support from the Dutch Research Council (NWO) and funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement 885065).","author":[{"first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Pieter Rein Ten","last_name":"Wolde","full_name":"Wolde, Pieter Rein Ten"}],"quality_controlled":"1","date_created":"2025-05-18T22:02:50Z","project":[{"name":"Efficient coding with biophysical realism","grant_number":"P34015","_id":"626c45b5-2b32-11ec-9570-e509828c1ba6"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation"},{"name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","grant_number":"101118866","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9"},{"name":"Information processing and computation in fish groups","grant_number":"RGP0065/2012","_id":"255008E4-B435-11E9-9278-68D0E5697425"}],"title":"Information processing in biochemical networks","external_id":{"isi":["001488641500013"],"pmid":["39929539"]},"publisher":"Annual Reviews","OA_type":"hybrid","article_processing_charge":"Yes (in subscription journal)","abstract":[{"text":"Living systems are characterized by controlled flows of matter, energy, and information. While the biophysics community has productively engaged with the first two, addressing information flows has been more challenging, with some scattered success in evolutionary theory and a more coherent track record in neuroscience. Nevertheless, interdisciplinary work of the past two decades at the interface of biophysics, quantitative biology, and engineering has led to an emerging mathematical language for describing information flows at the molecular scale. This is where the central processes of life unfold: from detection and transduction of environmental signals to the readout or copying of genetic information and the triggering of adaptive cellular responses. Such processes are coordinated by complex biochemical reaction networks that operate at room temperature, are out of equilibrium, and use low copy numbers of diverse molecular species with limited interaction specificity. Here we review how flows of information through biochemical networks can be formalized using information-theoretic quantities, quantified from data, and computed within various modeling frameworks. Optimization of information flows is presented as a candidate design principle that navigates the relevant time, energy, crosstalk, and metabolic constraints to predict reliable cellular signaling and gene regulation architectures built of individually noisy components.","lang":"eng"}],"year":"2025","publication_status":"published","doi":"10.1146/annurev-biophys-060524-102720","article_type":"original","month":"05","date_published":"2025-05-01T00:00:00Z","file":[{"file_name":"2025_AnnualReviewBiophysics_Tkacik.pdf","access_level":"open_access","file_size":317925,"date_updated":"2025-05-19T07:55:51Z","creator":"dernst","date_created":"2025-05-19T07:55:51Z","checksum":"9ab623b2bc45dcd5fdd2c9577ea8ae9f","content_type":"application/pdf","success":1,"relation":"main_file","file_id":"19710"}],"date_updated":"2026-08-12T09:25:42Z","day":"01","citation":{"apa":"Tkačik, G., &#38; Wolde, P. R. T. (2025). Information processing in biochemical networks. <i>Annual Review of Biophysics</i>. Annual Reviews. <a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">https://doi.org/10.1146/annurev-biophys-060524-102720</a>","short":"G. Tkačik, P.R.T. Wolde, Annual Review of Biophysics 54 (2025) 249–274.","chicago":"Tkačik, Gašper, and Pieter Rein Ten Wolde. “Information Processing in Biochemical Networks.” <i>Annual Review of Biophysics</i>. Annual Reviews, 2025. <a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">https://doi.org/10.1146/annurev-biophys-060524-102720</a>.","ieee":"G. Tkačik and P. R. T. Wolde, “Information processing in biochemical networks,” <i>Annual Review of Biophysics</i>, vol. 54. Annual Reviews, pp. 249–274, 2025.","ista":"Tkačik G, Wolde PRT. 2025. Information processing in biochemical networks. Annual Review of Biophysics. 54, 249–274.","mla":"Tkačik, Gašper, and Pieter Rein Ten Wolde. “Information Processing in Biochemical Networks.” <i>Annual Review of Biophysics</i>, vol. 54, Annual Reviews, 2025, pp. 249–74, doi:<a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">10.1146/annurev-biophys-060524-102720</a>.","ama":"Tkačik G, Wolde PRT. Information processing in biochemical networks. <i>Annual Review of Biophysics</i>. 2025;54:249-274. doi:<a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">10.1146/annurev-biophys-060524-102720</a>"},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}]}]