---
_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).
date_created: 2023-01-12T12:08:51Z
date_published: 2022-09-01T00:00:00Z
date_updated: 2023-02-13T09:20:34Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1016/j.coisb.2022.100435
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
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'
...
---
_id: '9018'
abstract:
- lang: eng
  text: Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved
    in histone dynamics during replication, transcription, and DNA repair. Overexpressed
    in proliferating tissues including many tumors, ASF1 has emerged as a promising
    therapeutic target. Here, we combine structural, computational, and biochemical
    approaches to design peptides that inhibit the ASF1-histone interaction. Starting
    from the structure of the human ASF1-histone complex, we developed a rational
    design strategy combining epitope tethering and optimization of interface contacts
    to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When
    introduced into cultured cells, the inhibitors impair cell proliferation, perturb
    cell-cycle progression, and reduce cell migration and invasion in a manner commensurate
    with their affinity for ASF1. Finally, we find that direct injection of the most
    potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results
    open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.
article_processing_charge: No
article_type: original
author:
- first_name: May M
  full_name: Bakail, May M
  id: FB3C3F8E-522F-11EA-B186-22963DDC885E
  last_name: Bakail
  orcid: 0000-0002-9592-1587
- first_name: Albane
  full_name: Gaubert, Albane
  last_name: Gaubert
- first_name: Jessica
  full_name: Andreani, Jessica
  last_name: Andreani
- first_name: Gwenaëlle
  full_name: Moal, Gwenaëlle
  last_name: Moal
- first_name: Guillaume
  full_name: Pinna, Guillaume
  last_name: Pinna
- first_name: Ekaterina
  full_name: Boyarchuk, Ekaterina
  last_name: Boyarchuk
- first_name: Marie-Cécile
  full_name: Gaillard, Marie-Cécile
  last_name: Gaillard
- first_name: Regis
  full_name: Courbeyrette, Regis
  last_name: Courbeyrette
- first_name: Carl
  full_name: Mann, Carl
  last_name: Mann
- first_name: Jean-Yves
  full_name: Thuret, Jean-Yves
  last_name: Thuret
- first_name: Bérengère
  full_name: Guichard, Bérengère
  last_name: Guichard
- first_name: Brice
  full_name: Murciano, Brice
  last_name: Murciano
- first_name: Nicolas
  full_name: Richet, Nicolas
  last_name: Richet
- first_name: Adeline
  full_name: Poitou, Adeline
  last_name: Poitou
- first_name: Claire
  full_name: Frederic, Claire
  last_name: Frederic
- first_name: Marie-Hélène
  full_name: Le Du, Marie-Hélène
  last_name: Le Du
- first_name: Morgane
  full_name: Agez, Morgane
  last_name: Agez
- first_name: Caroline
  full_name: Roelants, Caroline
  last_name: Roelants
- first_name: Zachary A.
  full_name: Gurard-Levin, Zachary A.
  last_name: Gurard-Levin
- first_name: Geneviève
  full_name: Almouzni, Geneviève
  last_name: Almouzni
- first_name: Nadia
  full_name: Cherradi, Nadia
  last_name: Cherradi
- first_name: Raphael
  full_name: Guerois, Raphael
  last_name: Guerois
- first_name: Françoise
  full_name: Ochsenbein, Françoise
  last_name: Ochsenbein
citation:
  ama: Bakail MM, Gaubert A, Andreani J, et al. Design on a rational basis of high-affinity
    peptides inhibiting the histone chaperone ASF1. <i>Cell Chemical Biology</i>.
    2019;26(11):1573-1585.e10. doi:<a href="https://doi.org/10.1016/j.chembiol.2019.09.002">10.1016/j.chembiol.2019.09.002</a>
  apa: Bakail, M. M., Gaubert, A., Andreani, J., Moal, G., Pinna, G., Boyarchuk, E.,
    … Ochsenbein, F. (2019). Design on a rational basis of high-affinity peptides
    inhibiting the histone chaperone ASF1. <i>Cell Chemical Biology</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.chembiol.2019.09.002">https://doi.org/10.1016/j.chembiol.2019.09.002</a>
  chicago: Bakail, May M, Albane Gaubert, Jessica Andreani, Gwenaëlle Moal, Guillaume
    Pinna, Ekaterina Boyarchuk, Marie-Cécile Gaillard, et al. “Design on a Rational
    Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” <i>Cell
    Chemical Biology</i>. Elsevier, 2019. <a href="https://doi.org/10.1016/j.chembiol.2019.09.002">https://doi.org/10.1016/j.chembiol.2019.09.002</a>.
  ieee: M. M. Bakail <i>et al.</i>, “Design on a rational basis of high-affinity peptides
    inhibiting the histone chaperone ASF1,” <i>Cell Chemical Biology</i>, vol. 26,
    no. 11. Elsevier, p. 1573–1585.e10, 2019.
  ista: Bakail MM, Gaubert A, Andreani J, Moal G, Pinna G, Boyarchuk E, Gaillard M-C,
    Courbeyrette R, Mann C, Thuret J-Y, Guichard B, Murciano B, Richet N, Poitou A,
    Frederic C, Le Du M-H, Agez M, Roelants C, Gurard-Levin ZA, Almouzni G, Cherradi
    N, Guerois R, Ochsenbein F. 2019. Design on a rational basis of high-affinity
    peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 26(11),
    1573–1585.e10.
  mla: Bakail, May M., et al. “Design on a Rational Basis of High-Affinity Peptides
    Inhibiting the Histone Chaperone ASF1.” <i>Cell Chemical Biology</i>, vol. 26,
    no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:<a href="https://doi.org/10.1016/j.chembiol.2019.09.002">10.1016/j.chembiol.2019.09.002</a>.
  short: M.M. Bakail, A. Gaubert, J. Andreani, G. Moal, G. Pinna, E. Boyarchuk, M.-C.
    Gaillard, R. Courbeyrette, C. Mann, J.-Y. Thuret, B. Guichard, B. Murciano, N.
    Richet, A. Poitou, C. Frederic, M.-H. Le Du, M. Agez, C. Roelants, Z.A. Gurard-Levin,
    G. Almouzni, N. Cherradi, R. Guerois, F. Ochsenbein, Cell Chemical Biology 26
    (2019) 1573–1585.e10.
date_created: 2021-01-19T11:04:50Z
date_published: 2019-11-21T00:00:00Z
date_updated: 2023-02-23T13:46:53Z
day: '21'
doi: 10.1016/j.chembiol.2019.09.002
extern: '1'
external_id:
  pmid:
  - '31543461'
intvolume: '        26'
issue: '11'
keyword:
- Clinical Biochemistry
- Molecular Medicine
- Biochemistry
- Molecular Biology
- Pharmacology
- Drug Discovery
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.chembiol.2019.09.002
month: '11'
oa: 1
oa_version: Published Version
page: 1573-1585.e10
pmid: 1
publication: Cell Chemical Biology
publication_identifier:
  issn:
  - 2451-9456
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: Design on a rational basis of high-affinity peptides inhibiting the histone
  chaperone ASF1
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 26
year: '2019'
...
---
_id: '13436'
abstract:
- lang: eng
  text: Cross-metathesis reactions of α,β-unsaturated sulfones and sulfoxides in the
    presence of molybdenum and ruthenium pre-catalysts were tested. A selective metahesis
    reaction was achieved between functionalized terminal olefins and vinyl sulfones
    by using the ‘second generation’ ruthenium catalysts 1c–h while the highly active
    Schrock catalyst 1b was found to be functional group incompatible with vinyl sulfones.
    The cross-metathesis products were isolated in good yields with an excellent (E)-selectivity.
    Both the molybdenum and ruthenium-based complexes were, however, incompatible
    with α,β- and β,γ-unsaturated sulfoxides.
article_processing_charge: No
article_type: original
author:
- first_name: Anna
  full_name: Michrowska, Anna
  last_name: Michrowska
- first_name: Michał
  full_name: Bieniek, Michał
  last_name: Bieniek
- first_name: Mikhail
  full_name: Kim, Mikhail
  last_name: Kim
- first_name: Rafal
  full_name: Klajn, Rafal
  id: 8e84690e-1e48-11ed-a02b-a1e6fb8bb53b
  last_name: Klajn
- first_name: Karol
  full_name: Grela, Karol
  last_name: Grela
citation:
  ama: Michrowska A, Bieniek M, Kim M, Klajn R, Grela K. Cross-metathesis reaction
    of vinyl sulfones and sulfoxides. <i>Tetrahedron</i>. 2003;59(25):4525-4531. doi:<a
    href="https://doi.org/10.1016/s0040-4020(03)00682-3">10.1016/s0040-4020(03)00682-3</a>
  apa: Michrowska, A., Bieniek, M., Kim, M., Klajn, R., &#38; Grela, K. (2003). Cross-metathesis
    reaction of vinyl sulfones and sulfoxides. <i>Tetrahedron</i>. Elsevier. <a href="https://doi.org/10.1016/s0040-4020(03)00682-3">https://doi.org/10.1016/s0040-4020(03)00682-3</a>
  chicago: Michrowska, Anna, Michał Bieniek, Mikhail Kim, Rafal Klajn, and Karol Grela.
    “Cross-Metathesis Reaction of Vinyl Sulfones and Sulfoxides.” <i>Tetrahedron</i>.
    Elsevier, 2003. <a href="https://doi.org/10.1016/s0040-4020(03)00682-3">https://doi.org/10.1016/s0040-4020(03)00682-3</a>.
  ieee: A. Michrowska, M. Bieniek, M. Kim, R. Klajn, and K. Grela, “Cross-metathesis
    reaction of vinyl sulfones and sulfoxides,” <i>Tetrahedron</i>, vol. 59, no. 25.
    Elsevier, pp. 4525–4531, 2003.
  ista: Michrowska A, Bieniek M, Kim M, Klajn R, Grela K. 2003. Cross-metathesis reaction
    of vinyl sulfones and sulfoxides. Tetrahedron. 59(25), 4525–4531.
  mla: Michrowska, Anna, et al. “Cross-Metathesis Reaction of Vinyl Sulfones and Sulfoxides.”
    <i>Tetrahedron</i>, vol. 59, no. 25, Elsevier, 2003, pp. 4525–31, doi:<a href="https://doi.org/10.1016/s0040-4020(03)00682-3">10.1016/s0040-4020(03)00682-3</a>.
  short: A. Michrowska, M. Bieniek, M. Kim, R. Klajn, K. Grela, Tetrahedron 59 (2003)
    4525–4531.
date_created: 2023-08-01T10:39:34Z
date_published: 2003-06-16T00:00:00Z
date_updated: 2023-08-08T12:44:17Z
day: '16'
doi: 10.1016/s0040-4020(03)00682-3
extern: '1'
intvolume: '        59'
issue: '25'
keyword:
- Organic Chemistry
- Drug Discovery
- Biochemistry
language:
- iso: eng
month: '06'
oa_version: None
page: 4525-4531
publication: Tetrahedron
publication_identifier:
  eissn:
  - 1464-5416
  issn:
  - 0040-4020
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cross-metathesis reaction of vinyl sulfones and sulfoxides
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 59
year: '2003'
...