---
_id: '15149'
abstract:
- lang: eng
  text: 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.
article_processing_charge: No
article_type: original
author:
- first_name: Luke
  full_name: Isbel, Luke
  last_name: Isbel
- first_name: Murat
  full_name: Iskar, Murat
  last_name: Iskar
- first_name: Sevi
  full_name: Durdu, Sevi
  last_name: Durdu
- first_name: Joscha
  full_name: Weiss, Joscha
  last_name: Weiss
- first_name: Ralph S.
  full_name: Grand, Ralph S.
  last_name: Grand
- first_name: Eric
  full_name: Hietter-Pfeiffer, Eric
  last_name: Hietter-Pfeiffer
- first_name: Zuzanna
  full_name: Kozicka, Zuzanna
  last_name: Kozicka
- first_name: Alicia
  full_name: Michael, Alicia
  id: 6437c950-2a03-11ee-914d-d6476dd7b75c
  last_name: Michael
  orcid: 0000-0002-6080-839X
- first_name: Lukas
  full_name: Burger, Lukas
  last_name: Burger
- first_name: Nicolas H.
  full_name: Thomä, Nicolas H.
  last_name: Thomä
- first_name: Dirk
  full_name: Schübeler, Dirk
  last_name: Schübeler
citation:
  ama: Isbel L, Iskar M, Durdu S, et al. Readout of histone methylation by Trim24
    locally restricts chromatin opening by p53. <i>Nature Structural &#38; Molecular
    Biology</i>. 2023;30(7):948-957. doi:<a href="https://doi.org/10.1038/s41594-023-01021-8">10.1038/s41594-023-01021-8</a>
  apa: Isbel, L., Iskar, M., Durdu, S., Weiss, J., Grand, R. S., Hietter-Pfeiffer,
    E., … Schübeler, D. (2023). Readout of histone methylation by Trim24 locally restricts
    chromatin opening by p53. <i>Nature Structural &#38; Molecular Biology</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41594-023-01021-8">https://doi.org/10.1038/s41594-023-01021-8</a>
  chicago: Isbel, Luke, Murat Iskar, Sevi Durdu, Joscha Weiss, Ralph S. Grand, Eric
    Hietter-Pfeiffer, Zuzanna Kozicka, et al. “Readout of Histone Methylation by Trim24
    Locally Restricts Chromatin Opening by P53.” <i>Nature Structural &#38; Molecular
    Biology</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41594-023-01021-8">https://doi.org/10.1038/s41594-023-01021-8</a>.
  ieee: L. Isbel <i>et al.</i>, “Readout of histone methylation by Trim24 locally
    restricts chromatin opening by p53,” <i>Nature Structural &#38; Molecular Biology</i>,
    vol. 30, no. 7. Springer Nature, pp. 948–957, 2023.
  ista: Isbel L, Iskar M, Durdu S, Weiss J, Grand RS, Hietter-Pfeiffer E, Kozicka
    Z, Michael AK, Burger L, Thomä NH, Schübeler D. 2023. Readout of histone methylation
    by Trim24 locally restricts chromatin opening by p53. Nature Structural &#38;
    Molecular Biology. 30(7), 948–957.
  mla: Isbel, Luke, et al. “Readout of Histone Methylation by Trim24 Locally Restricts
    Chromatin Opening by P53.” <i>Nature Structural &#38; Molecular Biology</i>, vol.
    30, no. 7, Springer Nature, 2023, pp. 948–57, doi:<a href="https://doi.org/10.1038/s41594-023-01021-8">10.1038/s41594-023-01021-8</a>.
  short: L. Isbel, M. Iskar, S. Durdu, J. Weiss, R.S. Grand, E. Hietter-Pfeiffer,
    Z. Kozicka, A.K. Michael, L. Burger, N.H. Thomä, D. Schübeler, Nature Structural
    &#38; Molecular Biology 30 (2023) 948–957.
date_created: 2024-03-21T07:53:24Z
date_published: 2023-06-29T00:00:00Z
date_updated: 2024-03-25T12:37:20Z
day: '29'
doi: 10.1038/s41594-023-01021-8
extern: '1'
external_id:
  pmid:
  - '37386214'
fulldoi: https://doi.org/10.1038/s41594-023-01021-8
intvolume: '        30'
issue: '7'
keyword:
- Molecular Biology
- Structural Biology
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41594-023-01021-8
month: '06'
oa: 1
oa_version: Published Version
page: 948-957
pmid: 1
publication: Nature Structural & Molecular Biology
publication_identifier:
  eissn:
  - 1545-9985
  issn:
  - 1545-9993
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Readout of histone methylation by Trim24 locally restricts chromatin opening
  by p53
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 30
year: '2023'
...