---
_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? Current Opinion in Systems Biology. 2022;31(9). doi:10.1016/j.coisb.2022.100435
apa: Zoller, B., Gregor, T., & Tkačik, G. (2022). Eukaryotic gene regulation
at equilibrium, or non? Current Opinion in Systems Biology. Elsevier. https://doi.org/10.1016/j.coisb.2022.100435
chicago: Zoller, Benjamin, Thomas Gregor, and Gašper Tkačik. “Eukaryotic Gene Regulation
at Equilibrium, or Non?” Current Opinion in Systems Biology. Elsevier,
2022. https://doi.org/10.1016/j.coisb.2022.100435.
ieee: B. Zoller, T. Gregor, and G. Tkačik, “Eukaryotic gene regulation at equilibrium,
or non?,” Current Opinion in Systems Biology, 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?”
Current Opinion in Systems Biology, vol. 31, no. 9, 100435, Elsevier, 2022,
doi:10.1016/j.coisb.2022.100435.
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
license: https://creativecommons.org/licenses/by/4.0/
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. Cell Chemical Biology.
2019;26(11):1573-1585.e10. doi:10.1016/j.chembiol.2019.09.002
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. Cell Chemical Biology. Elsevier.
https://doi.org/10.1016/j.chembiol.2019.09.002
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.” Cell
Chemical Biology. Elsevier, 2019. https://doi.org/10.1016/j.chembiol.2019.09.002.
ieee: M. M. Bakail et al., “Design on a rational basis of high-affinity peptides
inhibiting the histone chaperone ASF1,” Cell Chemical Biology, 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.” Cell Chemical Biology, vol. 26,
no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:10.1016/j.chembiol.2019.09.002.
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. Tetrahedron. 2003;59(25):4525-4531. doi:10.1016/s0040-4020(03)00682-3
apa: Michrowska, A., Bieniek, M., Kim, M., Klajn, R., & Grela, K. (2003). Cross-metathesis
reaction of vinyl sulfones and sulfoxides. Tetrahedron. Elsevier. https://doi.org/10.1016/s0040-4020(03)00682-3
chicago: Michrowska, Anna, Michał Bieniek, Mikhail Kim, Rafal Klajn, and Karol Grela.
“Cross-Metathesis Reaction of Vinyl Sulfones and Sulfoxides.” Tetrahedron.
Elsevier, 2003. https://doi.org/10.1016/s0040-4020(03)00682-3.
ieee: A. Michrowska, M. Bieniek, M. Kim, R. Klajn, and K. Grela, “Cross-metathesis
reaction of vinyl sulfones and sulfoxides,” Tetrahedron, 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.”
Tetrahedron, vol. 59, no. 25, Elsevier, 2003, pp. 4525–31, doi:10.1016/s0040-4020(03)00682-3.
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'
...