---
OA_place: publisher
OA_type: hybrid
_id: '22363'
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.
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.)
article_number: e2524855123
article_processing_charge: Yes
article_type: original
author:
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Alexis
full_name: Benichou, Alexis
id: 3a67230c-5fc0-11ef-a673-de9a2ffadafe
last_name: Benichou
- first_name: Thomas
full_name: Gregor, Thomas
last_name: Gregor
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Zoller B, Benichou A, Gregor T, Tkačik G. Invariant nonequilibrium dynamics
in gene regulation optimize information flow. Proceedings of the National Academy
of Sciences of the United States of America. 2026;123(28). doi:10.1073/pnas.2524855123
apa: 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. National Academy of Sciences.
https://doi.org/10.1073/pnas.2524855123
chicago: Zoller, Benjamin, Alexis Benichou, Thomas Gregor, and Gašper Tkačik. “Invariant
Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” Proceedings
of the National Academy of Sciences of the United States of America. National
Academy of Sciences, 2026. https://doi.org/10.1073/pnas.2524855123.
ieee: B. Zoller, A. Benichou, T. Gregor, and G. Tkačik, “Invariant nonequilibrium
dynamics in gene regulation optimize information flow,” Proceedings of the
National Academy of Sciences of the United States of America, vol. 123, no.
28. National Academy of Sciences, 2026.
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.” Proceedings of the National Academy of Sciences
of the United States of America, vol. 123, no. 28, e2524855123, National Academy
of Sciences, 2026, doi:10.1073/pnas.2524855123.
short: B. Zoller, A. Benichou, T. Gregor, G. Tkačik, Proceedings of the National
Academy of Sciences of the United States of America 123 (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Software code data have been deposited in Institute Pasteur
GitHub (https://gitlab.pasteur.fr/tglab/invariantpromoterdynamicspaper) (51).
date_created: 2026-07-19T22:01:46Z
date_published: 2026-07-14T00:00:00Z
date_updated: 2026-07-20T13:15:11Z
day: '14'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.2524855123
external_id:
pmid:
- '42406962'
file:
- access_level: open_access
checksum: f4d82dd706ff1629db68d71190288350
content_type: application/pdf
creator: dernst
date_created: 2026-07-20T13:12:47Z
date_updated: 2026-07-20T13:12:47Z
file_id: '22376'
file_name: 2026_PNAS_Zoller.pdf
file_size: 24580098
relation: main_file
success: 1
file_date_updated: 2026-07-20T13:12:47Z
has_accepted_license: '1'
intvolume: ' 123'
issue: '28'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
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'
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Invariant nonequilibrium dynamics in gene regulation optimize information flow
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 123
year: '2026'
...