---
_id: '12156'
abstract:
- lang: eng
  text: Models of transcriptional regulation that assume equilibrium binding of transcription
    factors have been less successful at predicting gene expression from sequence
    in eukaryotes than in bacteria. This could be due to the non-equilibrium nature
    of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium
    mechanisms is vast and predominantly uninteresting. The key question is therefore
    how this space can be navigated efficiently, to focus on mechanisms and models
    that are biologically relevant. In this review, we advocate for the normative
    role of theory—theory that prescribes rather than just describes—in providing
    such a focus. Theory should expand its remit beyond inferring mechanistic models
    from data, towards identifying non-equilibrium gene regulatory schemes that may
    have been evolutionarily selected, despite their energy consumption, because they
    are precise, reliable, fast, or otherwise outperform regulation at equilibrium.
    We illustrate our reasoning by toy examples for which we provide simulation code.
acknowledgement: 'This work was supported through the Center for the Physics of Biological
  Function (PHYe1734030) and by National Institutes of Health Grants R01GM097275 and
  U01DK127429 (TG). GT acknowledges the support of the Austrian Science Fund grant
  FWF P28844 and the Human Frontiers Science Program. '
article_number: '100435'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Benjamin
  full_name: Zoller, Benjamin
  last_name: Zoller
- 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: '1'
citation:
  ama: Zoller B, Gregor T, Tkačik G. Eukaryotic gene regulation at equilibrium, or
    non? <i>Current Opinion in Systems Biology</i>. 2022;31(9). doi:<a href="https://doi.org/10.1016/j.coisb.2022.100435">10.1016/j.coisb.2022.100435</a>
  apa: Zoller, B., Gregor, T., &#38; Tkačik, G. (2022). Eukaryotic gene regulation
    at equilibrium, or non? <i>Current Opinion in Systems Biology</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.coisb.2022.100435">https://doi.org/10.1016/j.coisb.2022.100435</a>
  chicago: Zoller, Benjamin, Thomas Gregor, and Gašper Tkačik. “Eukaryotic Gene Regulation
    at Equilibrium, or Non?” <i>Current Opinion in Systems Biology</i>. Elsevier,
    2022. <a href="https://doi.org/10.1016/j.coisb.2022.100435">https://doi.org/10.1016/j.coisb.2022.100435</a>.
  ieee: B. Zoller, T. Gregor, and G. Tkačik, “Eukaryotic gene regulation at equilibrium,
    or non?,” <i>Current Opinion in Systems Biology</i>, vol. 31, no. 9. Elsevier,
    2022.
  ista: Zoller B, Gregor T, Tkačik G. 2022. Eukaryotic gene regulation at equilibrium,
    or non? Current Opinion in Systems Biology. 31(9), 100435.
  mla: Zoller, Benjamin, et al. “Eukaryotic Gene Regulation at Equilibrium, or Non?”
    <i>Current Opinion in Systems Biology</i>, vol. 31, no. 9, 100435, Elsevier, 2022,
    doi:<a href="https://doi.org/10.1016/j.coisb.2022.100435">10.1016/j.coisb.2022.100435</a>.
  short: B. Zoller, T. Gregor, G. Tkačik, Current Opinion in Systems Biology 31 (2022).
corr_author: '1'
date_created: 2023-01-12T12:08:51Z
date_published: 2022-09-01T00:00:00Z
date_updated: 2025-06-11T13:47:43Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1016/j.coisb.2022.100435
external_id:
  pmid:
  - '36590072'
file:
- access_level: open_access
  checksum: 97ef01e0cc60cdc84f45640a0f248fb0
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-24T12:14:10Z
  date_updated: 2023-01-24T12:14:10Z
  file_id: '12362'
  file_name: 2022_CurrentBiology_Zoller.pdf
  file_size: 2214944
  relation: main_file
  success: 1
file_date_updated: 2023-01-24T12:14:10Z
has_accepted_license: '1'
intvolume: '        31'
issue: '9'
keyword:
- Applied Mathematics
- Computer Science Applications
- Drug Discovery
- General Biochemistry
- Genetics and Molecular Biology
- Modeling and Simulation
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: Current Opinion in Systems Biology
publication_identifier:
  issn:
  - 2452-3100
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Eukaryotic gene regulation at equilibrium, or non?
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 31
year: '2022'
...