@article{21509,
abstract = {Chromatin remodeling complexes mobilize nucleosomes and promote transcription factor (TF) binding. Using ensemble and single-molecule assays combined with cryo-electron microscopy (cryo-EM), we studied the interaction between pioneer TFs OCT4–SOX2 and the human BRG1/BRM-associated factor (BAF) complex on nucleosomes. BAF engages TF-bound substrates in two orientations, placing OCT4–SOX2 at either the remodeler ENTRY or EXIT site. At the ENTRY site, OCT4–SOX2 initially coexists with BAF without structural interference. However, continued DNA translocation is expected to cause collisions with bound TFs, which can trigger remodeling direction reversals or may induce TF dissociation. To accommodate TFs at the EXIT site, BAF undergoes structural rearrangements, and ensemble assays reveal a nucleosome subpopulation translocating away from TF-binding sites. Moreover, single-molecule experiments show that nucleosome-bound BAF frequently changes remodeling direction, and we identify an ADP-bound remodeler conformation as a potential intermediate. Together, these findings reveal key aspects of the conformational dynamics and remodeling outcomes underlying BAF processing of TF-bound nucleosomes.},
author = {Weiss, Joscha and Vecchia, Luca and Domjan, David and Cavadini, Simone and Sabantsev, Anton and Kempf, Georg and Pathare, Ganesh R. and Brackmann, Klaus and Michael, Alicia and Kater, Lukas and Hietter-Pfeiffer, Eric and Haddawi, Mina and Kuber, Urja P. and Mühlhäusser, Sandra and Grand, Ralph S. and Stadler, Michael B. and Deindl, Sebastian and Thomä, Nicolas H.},
issn = {1097-2765},
journal = {Molecular Cell},
number = {4},
pages = {625--639.e8},
publisher = {Elsevier},
title = {{The human BAF chromatin remodeler processes nucleosomes bound by pioneer transcription factors OCT4–SOX2}},
doi = {10.1016/j.molcel.2026.01.021},
volume = {86},
year = {2026},
}
@article{20924,
abstract = {Pioneer transcription factors (TFs) possess the ability to read out DNA motifs embedded within nucleosomes, driving changes in gene expression during cellular differentiation and reprogramming. Here, we present selected engagement on nucleosome sequencing (SeEN-seq), a protocol designed to systematically identify potential TF-binding sites on the nucleosome. We describe steps for nucleosome library assembly, SeEN-seq assay, and cryoelectron microscopy (cryo-EM) sample preparation. This protocol facilitates the preparation of homogeneous pioneer TF-nucleosome complexes for cryo-EM structure determination using single-particle analysis.
For complete details on the use and execution of this protocol, please refer to Michael et al.1},
author = {Kobayashi, Wataru and Michael, Alicia and Ruangroengkulrith, Siwat and Kümmecke, Maximilian and Tachibana, Kikuë},
issn = {2666-1667},
journal = {STAR Protocols},
number = {1},
publisher = {Elsevier},
title = {{Protocol for integrative analysis of transcription factor-nucleosome interactions using SeEN-seq and cryo-EM structure determination}},
doi = {10.1016/j.xpro.2025.104295},
volume = {7},
year = {2026},
}
@article{20935,
abstract = {In situ cryo-electron tomography (cryo-ET) has emerged as the method of choice to investigate the structures of biomolecules in their native context. However, challenges remain for the efficient production and sharing of large-scale cryo-ET datasets. Here, we combined cryogenic plasma-based focused ion beam (cryo-PFIB) milling with recent advances in cryo-ET acquisition and processing to generate a dataset of 1,829 annotated tomograms of the green alga Chlamydomonas reinhardtii, which we provide as a community resource to drive method development and inspire biological discovery. To assay data quality, we performed subtomogram averaging of both soluble and membrane-bound complexes ranging in size from >3 MDa to ∼200 kDa, including 80S ribosomes, Rubisco, nucleosomes, microtubules, clathrin, photosystem II, and mitochondrial ATP synthase. The majority of these density maps reached sub-nanometer resolution, demonstrating the potential of this C. reinhardtii dataset as well as the promise of modern cryo-ET workflows and open data sharing to empower visual proteomics.},
author = {Kelley, Ron and Khavnekar, Sagar and Righetto, Ricardo D. and Heebner, Jessica and Obr, Martin and Zhang, Xianjun and Chakraborty, Saikat and Tagiltsev, Grigory and Michael, Alicia and Van Dorst, Sofie and Waltz, Florent and Mccafferty, Caitlyn L. and Lamm, Lorenz and Zufferey, Simon and Van Der Stappen, Philippe and Van Den Hoek, Hugo and Wietrzynski, Wojciech and Harar, Pavol and Wan, William and Briggs, John A.G. and Plitzko, Jürgen M. and Engel, Benjamin D. and Kotecha, Abhay},
issn = {1097-4164},
journal = {Molecular Cell},
number = {1},
pages = {213--230.e7},
publisher = {Elsevier},
title = {{Toward community-driven visual proteomics with large-scale cryo-electron tomography of Chlamydomonas reinhardtii}},
doi = {10.1016/j.molcel.2025.11.029},
volume = {86},
year = {2026},
}
@article{22720,
abstract = {Circadian clocks underlie daily rhythms in physiology by coordinating temporal patterns of gene expression and protein function throughout the body. At the core of this system in mammals is CLOCK/BMAL1, a ubiquitously expressed heterodimeric transcription factor complex that orchestrates tissue-specific circadian gene expression. The basis for this specificity remains unclear, but tissue-specific interactions at chromatin could provide one. Here we used chromatin immunoprecipitation coupled to mass spectrometry to map CLOCK/BMAL1-associated protein complexes on chromatin in mouse liver, kidney and lung. We detected 1,510 associated proteins, most of which were tissue-specific and not explained by protein abundance. Among these, we identified the homeodomain transcription factors PROX1, HNF1B and HOXA5 as tissue-enriched interactors that bind BMAL1, co-occupy most BMAL1 genomic sites and establish organ-restricted circadian transcription. Our findings demonstrate that tissue-specific transcription factors confer cellular identity on the core clock, thereby contributing to organ-specific patterns of rhythmic gene expression.},
author = {Aygenli, Fatih and Huschet, Lukas A. and Popp, Tanja and Ribeiro, Andrea and Barkhatova, Darina and Jouffe, Céline and Trozzo, Ricardo and Menet, Jerome S. and Rad, Roland and Dyar, Kenneth A. and Lech, Maciej and Straub, Tobias and Michael, Alicia and Robles, Maria S.},
issn = {1476-4679},
journal = {Nature Cell Biology},
publisher = {Springer Nature},
title = {{CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators}},
doi = {10.1038/s41556-026-02041-4},
year = {2026},
}
@article{20374,
abstract = {Pioneer transcription factors (TFs) engage chromatinized DNA motifs. However, it is unclear how the resultant TF-nucleosome complexes are decoded by co-factors. In humans, the TF p53 regulates cell-cycle progression, apoptosis, and the DNA damage response, with a large fraction of p53-bound sites residing in nucleosome-harboring inaccessible chromatin. We examined the interaction of chromatin-bound p53 with co-factors belonging to the ubiquitin proteasome system (UPS). At two distinct motif locations on the nucleosome (super-helical location [SHL]−5.7 and SHL+5.9), the E3 ubiquitin ligase E6-E6AP was unable to bind nucleosome-engaged p53. The deubiquitinase USP7, on the other hand, readily engages nucleosome-bound p53 in vitro and in cells. A corresponding cryo-electron microscopy (cryo-EM) structure shows USP7 engaged with p53 and nucleosomes. Our work illustrates how chromatin imposes a co-factor-selective barrier for p53 interactors, whereby flexibly tethered interaction domains of co-factors and TFs govern compatibility between co-factors, TFs, and chromatin.},
author = {Chakraborty, Deyasini and Sandate, Colby R. and Isbel, Luke and Kempf, Georg and Weiss, Joscha and Cavadini, Simone and Kater, Lukas and Seebacher, Jan and Kozicka, Zuzanna and Stoos, Lisa and Grand, Ralph S. and Schübeler, Dirk and Michael, Alicia and Thomä, Nicolas H.},
issn = {1097-2765},
journal = {Molecular Cell},
number = {15},
pages = {2919--2936.e12},
publisher = {Elsevier},
title = {{Nucleosomes specify co-factor access to p53}},
doi = {10.1016/j.molcel.2025.06.027},
volume = {85},
year = {2025},
}
@article{15148,
abstract = {The basic helix–loop–helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members1. Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX and the circadian transcription factor CLOCK-BMAL1 (refs. 2,3). Both transcription factors bind to E-boxes preferentially near the nucleosomal entry–exit sites. Structural studies with engineered or native nucleosome sequences show that MYC-MAX or CLOCK-BMAL1 triggers the release of DNA from histones to gain access. Atop the H2A–H2B acidic patch4, the CLOCK-BMAL1 Per-Arnt-Sim (PAS) dimerization domains engage the histone octamer disc. Binding of tandem E-boxes5–7 at endogenous DNA sequences occurs through direct interactions between two CLOCK-BMAL1 protomers and histones and is important for circadian cycling. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B and H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerization domain jointly determine the histone contact, the affinity and the degree of competition and cooperativity with other nucleosome-bound factors.},
author = {Michael, Alicia and Stoos, Lisa and Crosby, Priya and Eggers, Nikolas and Nie, Xinyu Y. and Makasheva, Kristina and Minnich, Martina and Healy, Kelly L. and Weiss, Joscha and Kempf, Georg and Cavadini, Simone and Kater, Lukas and Seebacher, Jan and Vecchia, Luca and Chakraborty, Deyasini and Isbel, Luke and Grand, Ralph S. and Andersch, Florian and Fribourgh, Jennifer L. and Schübeler, Dirk and Zuber, Johannes and Liu, Andrew C. and Becker, Peter B. and Fierz, Beat and Partch, Carrie L. and Menet, Jerome S. and Thomä, Nicolas H.},
issn = {1476-4687},
journal = {Nature},
number = {7969},
pages = {385--393},
publisher = {Springer Nature},
title = {{Cooperation between bHLH transcription factors and histones for DNA access}},
doi = {10.1038/s41586-023-06282-3},
volume = {619},
year = {2023},
}
@article{15149,
abstract = {The genomic binding sites of the transcription factor (TF) and tumor suppressor p53 are unusually diverse with regard to their chromatin features, including histone modifications, raising the possibility that the local chromatin environment can contextualize p53 regulation. Here, we show that epigenetic characteristics of closed chromatin, such as DNA methylation, do not influence the binding of p53 across the genome. Instead, the ability of p53 to open chromatin and activate its target genes is locally restricted by its cofactor Trim24. Trim24 binds to both p53 and unmethylated histone 3 lysine 4 (H3K4), thereby preferentially localizing to those p53 sites that reside in closed chromatin, whereas it is deterred from accessible chromatin by H3K4 methylation. The presence of Trim24 increases cell viability upon stress and enables p53 to affect gene expression as a function of the local chromatin state. These findings link H3K4 methylation to p53 function and illustrate how specificity in chromatin can be achieved, not by TF-intrinsic sensitivity to histone modifications, but by employing chromatin-sensitive cofactors that locally modulate TF function.},
author = {Isbel, Luke and Iskar, Murat and Durdu, Sevi and Weiss, Joscha and Grand, Ralph S. and Hietter-Pfeiffer, Eric and Kozicka, Zuzanna and Michael, Alicia and Burger, Lukas and Thomä, Nicolas H. and Schübeler, Dirk},
issn = {1545-9985},
journal = {Nature Structural & Molecular Biology},
keywords = {Molecular Biology, Structural Biology},
number = {7},
pages = {948--957},
publisher = {Springer Nature},
title = {{Readout of histone methylation by Trim24 locally restricts chromatin opening by p53}},
doi = {10.1038/s41594-023-01021-8},
volume = {30},
year = {2023},
}
@article{15150,
abstract = {The majority of gene transcripts generated by RNA polymerase II in mammalian genomes initiate at CpG island (CGI) promoters1,2, yet our understanding of their regulation remains limited. This is in part due to the incomplete information that we have on transcription factors, their DNA-binding motifs and which genomic binding sites are functional in any given cell type3,4,5. In addition, there are orphan motifs without known binders, such as the CGCG element, which is associated with highly expressed genes across human tissues and enriched near the transcription start site of a subset of CGI promoters6,7,8. Here we combine single-molecule footprinting with interaction proteomics to identify BTG3-associated nuclear protein (BANP) as the transcription factor that binds this element in the mouse and human genome. We show that BANP is a strong CGI activator that controls essential metabolic genes in pluripotent stem and terminally differentiated neuronal cells. BANP binding is repelled by DNA methylation of its motif in vitro and in vivo, which epigenetically restricts most binding to CGIs and accounts for differential binding at aberrantly methylated CGI promoters in cancer cells. Upon binding to an unmethylated motif, BANP opens chromatin and phases nucleosomes. These findings establish BANP as a critical activator of a set of essential genes and suggest a model in which the activity of CGI promoters relies on methylation-sensitive transcription factors that are capable of chromatin opening.},
author = {Grand, Ralph S. and Burger, Lukas and Gräwe, Cathrin and Michael, Alicia and Isbel, Luke and Hess, Daniel and Hoerner, Leslie and Iesmantavicius, Vytautas and Durdu, Sevi and Pregnolato, Marco and Krebs, Arnaud R. and Smallwood, Sébastien A. and Thomä, Nicolas and Vermeulen, Michiel and Schübeler, Dirk},
issn = {1476-4687},
journal = {Nature},
pages = {133--137},
publisher = {Springer Nature},
title = {{BANP opens chromatin and activates CpG-island-regulated genes}},
doi = {10.1038/s41586-021-03689-8},
volume = {596},
year = {2021},
}
@article{15151,
abstract = {Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone core, thereby rendering a large fraction of the DNA surface inaccessible to DNA-binding proteins. Nevertheless, first responders in DNA repair and sequence-specific transcription factors bind DNA target sites obstructed by chromatin. While early studies examined protein binding to histone-free DNA, it is only now beginning to emerge how DNA sequences are interrogated on nucleosomes. These readout strategies range from the release of nucleosomal DNA from histones, to rotational/translation register shifts of the DNA motif, and nucleosome-specific DNA binding modes that differ from those observed on naked DNA. Since DNA motif engagement on nucleosomes strongly depends on position and orientation, we argue that motif location and nucleosome positioning co-determine protein access to DNA in transcription and DNA repair.},
author = {Michael, Alicia and Thomä, Nicolas H.},
issn = {0092-8674},
journal = {Cell},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {14},
pages = {3599--3611},
publisher = {Elsevier},
title = {{Reading the chromatinized genome}},
doi = {10.1016/j.cell.2021.05.029},
volume = {184},
year = {2021},
}
@article{15152,
abstract = {Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo–electron microscopy at two preferred positions. Depending on motif location, OCT4 and SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from histone H2A and histone H3; however, at an inverted motif, the TFs only induce local DNA distortions. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures, reading out a partial motif. These findings explain site-specific nucleosome engagement by the pluripotency factors OCT4 and SOX2, and they reveal how TFs distort nucleosomes to access chromatinized motifs.},
author = {Michael, Alicia Kathleen and Grand, Ralph S. and Isbel, Luke and Cavadini, Simone and Kozicka, Zuzanna and Kempf, Georg and Bunker, Richard D. and Schenk, Andreas D. and Graff-Meyer, Alexandra and Pathare, Ganesh R. and Weiss, Joscha and Matsumoto, Syota and Burger, Lukas and Schübeler, Dirk and Thomä, Nicolas H.},
issn = {1095-9203},
journal = {Science},
number = {6498},
pages = {1460--1465},
publisher = {American Association for the Advancement of Science },
title = {{Mechanisms of OCT4-SOX2 motif readout on nucleosomes}},
doi = {10.1126/science.abb0074},
volume = {368},
year = {2020},
}
@article{15153,
abstract = {Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.},
author = {Fribourgh, Jennifer L and Srivastava, Ashutosh and Sandate, Colby R and Michael, Alicia Kathleen and Hsu, Peter L and Rakers, Christin and Nguyen, Leslee T and Torgrimson, Megan R and Parico, Gian Carlo G and Tripathi, Sarvind and Zheng, Ning and Lander, Gabriel C and Hirota, Tsuyoshi and Tama, Florence and Partch, Carrie L},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing}},
doi = {10.7554/elife.55275},
volume = {9},
year = {2020},
}
@unpublished{15147,
abstract = {Circadian rhythms are generated by a transcription-based feedback loop where CLOCK:BMAL1 drive transcription of their repressors (PER1/2, CRY1/2), which bind to CLOCK:BMAL1 to close the feedback loop with ~24-hour periodicity. Here we identify a key biochemical and structural difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. While both cryptochromes bind the BMAL1 transactivation domain with similar affinity to sequester it from coactivators, CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We identify a dynamic loop in the secondary pocket that regulates differential binding of cryptochromes to the PAS domain core. Notably, PER2 binding remodels this loop in CRY2 to enhance its affinity for CLOCK:BMAL1, explaining why CRY2 forms an obligate heterodimer with PER2, while CRY1 is capable of repressing CLOCK:BMAL1 both with and without PER2.},
author = {Fribourgh, Jennifer L. and Srivastava, Ashutosh and Sandate, Colby R. and Michael, Alicia and Hsu, Peter L. and Rakers, Christin and Nguyen, Leslee T. and Torgrimson, Megan R. and Parico, Gian Carlo G. and Tripathi, Sarvind and Zheng, Ning and Lander, Gabriel C. and Hirota, Tsuyoshi and Tama, Florence and Partch, Carrie L.},
booktitle = {bioRxiv},
title = {{Protein dynamics regulate distinct biochemical properties of cryptochromes in mammalian circadian rhythms}},
doi = {10.1101/740464},
year = {2019},
}
@article{15154,
abstract = {Biofilm formation is critical for the infection cycle of Vibrio cholerae. Vibrio exopolysaccharides (VPS) and the matrix proteins RbmA, Bap1 and RbmC are required for the development of biofilm architecture. We demonstrate that RbmA binds VPS directly and uses a binary structural switch within its first fibronectin type III (FnIII-1) domain to control RbmA structural dynamics and the formation of VPS-dependent higher-order structures. The structural switch in FnIII-1 regulates interactions in trans with the FnIII-2 domain, leading to open (monomeric) or closed (dimeric) interfaces. The ability of RbmA to switch between open and closed states is important for V. cholerae biofilm formation, as RbmA variants with switches that are locked in either of the two states lead to biofilms with altered architecture and structural integrity.},
author = {Fong, Jiunn CN and Rogers, Andrew and Michael, Alicia Kathleen and Parsley, Nicole C and Cornell, William-Cole and Lin, Yu-Cheng and Singh, Praveen K and Hartmann, Raimo and Drescher, Knut and Vinogradov, Evgeny and Dietrich, Lars EP and Partch, Carrie L and Yildiz, Fitnat H},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms}},
doi = {10.7554/elife.26163},
volume = {6},
year = {2017},
}
@article{15155,
abstract = {The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination.},
author = {Gustafson, Chelsea L. and Parsley, Nicole C. and Asimgil, Hande and Lee, Hsiau-Wei and Ahlbach, Christopher and Michael, Alicia Kathleen and Xu, Haiyan and Williams, Owen L. and Davis, Tara L. and Liu, Andrew C. and Partch, Carrie L.},
issn = {1097-2765},
journal = {Molecular Cell},
keywords = {Cell Biology, Molecular Biology},
number = {4},
pages = {447--457.e7},
publisher = {Elsevier},
title = {{A slow conformational switch in the BMAL1 transactivation domain modulates circadian rhythms}},
doi = {10.1016/j.molcel.2017.04.011},
volume = {66},
year = {2017},
}
@article{15156,
abstract = {Circadian clocks are ubiquitous timing systems that induce rhythms of biological activities in synchrony with night and day. In cyanobacteria, timing is generated by a posttranslational clock consisting of KaiA, KaiB, and KaiC proteins and a set of output signaling proteins, SasA and CikA, which transduce this rhythm to control gene expression. Here, we describe crystal and nuclear magnetic resonance structures of KaiB-KaiC,KaiA-KaiB-KaiC, and CikA-KaiB complexes. They reveal how the metamorphic properties of KaiB, a protein that adopts two distinct folds, and the post–adenosine triphosphate hydrolysis state of KaiC create a hub around which nighttime signaling events revolve, including inactivation of KaiA and reciprocal regulation of the mutually antagonistic signaling proteins, SasA and CikA.},
author = {Tseng, Roger and Goularte, Nicolette F. and Chavan, Archana and Luu, Jansen and Cohen, Susan E. and Chang, Yong-Gang and Heisler, Joel and Li, Sheng and Michael, Alicia Kathleen and Tripathi, Sarvind and Golden, Susan S. and LiWang, Andy and Partch, Carrie L.},
issn = {1095-9203},
journal = {Science},
keywords = {Multidisciplinary},
number = {6330},
pages = {1174--1180},
publisher = {American Association for the Advancement of Science},
title = {{Structural basis of the day-night transition in a bacterial circadian clock}},
doi = {10.1126/science.aag2516},
volume = {355},
year = {2017},
}
@article{15157,
abstract = {The basic helix–loop–helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ∼24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here we show that CRY1 binds directly to the PAS domain core of CLOCK:BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.},
author = {Michael, Alicia Kathleen and Fribourgh, Jennifer L. and Chelliah, Yogarany and Sandate, Colby R. and Hura, Greg L. and Schneidman-Duhovny, Dina and Tripathi, Sarvind M. and Takahashi, Joseph S. and Partch, Carrie L.},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences},
keywords = {Multidisciplinary},
number = {7},
pages = {1560--1565},
publisher = {Proceedings of the National Academy of Sciences},
title = {{Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1}},
doi = {10.1073/pnas.1615310114},
volume = {114},
year = {2017},
}
@article{15158,
abstract = {Cryptochromes are evolutionarily related to the light‐dependent DNA repair enzyme photolyase, serving as major regulators of circadian rhythms in insects and vertebrate animals. There are two types of cryptochromes in the animal kingdom: Drosophila‐like CRYs that act as nonvisual photopigments linking circadian rhythms to the environmental light/dark cycle, and vertebrate‐like CRYs that do not appear to sense light directly, but control the generation of circadian rhythms by acting as transcriptional repressors. Some animals have both types of CRYs, while others possess only one. Cryptochromes have two domains, the photolyase homology region (PHR) and an extended, intrinsically disordered C‐terminus. While all animal CRYs share a high degree of sequence and structural homology in their PHR domains, the C‐termini are divergent in both length and sequence identity. Recently, cryptochrome function has been shown to extend beyond its pivotal role in circadian clocks, participating in regulation of the DNA damage response, cancer progression and glucocorticoid signaling, as well as being implicated as possible magnetoreceptors. In this review, we provide a historical perspective on the discovery of animal cryptochromes, examine similarities and differences of the two types of animal cryptochromes and explore some of the divergent roles for this class of proteins.},
author = {Michael, Alicia Kathleen and Fribourgh, Jennifer L. and Van Gelder, Russell N. and Partch, Carrie L.},
issn = {1751-1097},
journal = {Photochemistry and Photobiology},
keywords = {Physical and Theoretical Chemistry, General Medicine, Biochemistry},
number = {1},
pages = {128--140},
publisher = {Wiley},
title = {{Animal cryptochromes: Divergent roles in light perception, circadian timekeeping and beyond}},
doi = {10.1111/php.12677},
volume = {93},
year = {2017},
}
@article{15159,
abstract = {It is widely recognized that BMAL1 is an essential subunit of the primary transcription factor that drives rhythmic circadian transcription in the nucleus. In a surprising turn, Lipton et al. now show that BMAL1 rhythmically interacts with translational machinery in the cytosol to stimulate protein synthesis in response to mTOR signaling.},
author = {Michael, Alicia Kathleen and Asimgil, Hande and Partch, Carrie L.},
issn = {0968-0004},
journal = {Trends in Biochemical Sciences},
keywords = {Molecular Biology, Biochemistry},
number = {9},
pages = {489--490},
publisher = {Elsevier},
title = {{Cytosolic BMAL1 moonlights as a translation factor}},
doi = {10.1016/j.tibs.2015.07.006},
volume = {40},
year = {2015},
}
@article{15160,
abstract = {The circadian clock orchestrates global changes in transcriptional regulation on a daily basis via the bHLH-PAS transcription factor CLOCK:BMAL1. Pathways driven by other bHLH-PAS transcription factors have a homologous repressor that modulates activity on a tissue-specific basis, but none have been identified for CLOCK:BMAL1. We show here that the cancer/testis antigen PASD1 fulfills this role to suppress circadian rhythms. PASD1 is evolutionarily related to CLOCK and interacts with the CLOCK:BMAL1 complex to repress transcriptional activation. Expression of PASD1 is restricted to germline tissues in healthy individuals but can be induced in cells of somatic origin upon oncogenic transformation. Reducing PASD1 in human cancer cells significantly increases the amplitude of transcriptional oscillations to generate more robust circadian rhythms. Our results describe a function for a germline-specific protein in regulation of the circadian clock and provide a molecular link from oncogenic transformation to suppression of circadian rhythms.},
author = {Michael, Alicia Kathleen and Harvey, Stacy L. and Sammons, Patrick J. and Anderson, Amanda P. and Kopalle, Hema M. and Banham, Alison H. and Partch, Carrie L.},
issn = {1097-2765},
journal = {Molecular Cell},
keywords = {Cell Biology, Molecular Biology},
number = {5},
pages = {743--754},
publisher = {Elsevier},
title = {{Cancer/Testis antigen PASD1 silences the circadian clock}},
doi = {10.1016/j.molcel.2015.03.031},
volume = {58},
year = {2015},
}
@article{15161,
abstract = {The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry.},
author = {Guan, Weiye and Michael, Alicia Kathleen and McIntosh, Melissa L. and Koren-Selfridge, Liza and Scott, John P. and Clark, Timothy B.},
issn = {1520-6904},
journal = {The Journal of Organic Chemistry},
keywords = {Organic Chemistry},
number = {15},
pages = {7199--7204},
publisher = {American Chemical Society},
title = {{Stereoselective formation of trisubstituted vinyl boronate esters by the acid-mediated elimination of α-hydroxyboronate esters}},
doi = {10.1021/jo500773t},
volume = {79},
year = {2014},
}