Dataset Information

Readout of histone methylation by Trim24 locally restricts chromatin opening by p53

ABSTRACT: The genomic binding sites of the transcription factor (TF) and tumour suppressor p53 are unusually diverse in regards to their chromatin features, including histone modifications, opening the possibility that chromatin provides context-dependence for p53 regulation. Here, we show that the ability of p53 to open chromatin and activate its target genes is indeed locally restricted by its cofactor Trim24. Trim24 binds to both p53 and unmethylated lysine 4 of histone H3, thereby preferentially locating to those p53 sites that reside in closed chromatin, while it is deterred from accessible chromatin by lysine 4 methylation. The presence of Trim24 increases cell viability upon stress and enables p53 to impact gene expression as a function of the local chromatin state. These findings link histone 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 which locally modulate TF function.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Early Embryonic Cell

SUBMITTER: Daniel Hess

LAB HEAD: Dr. Dirk Schuebeler

PROVIDER: PXD039553 | Pride | 2023-05-05

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	L3_220701_DH_3197_A4h_S04.raw	Raw
	L3_220701_DH_3197_A4h_S05.raw	Raw
	L3_220701_DH_3197_A4h_S06.raw	Raw
	L3_220701_DH_3197_DA4h_S07.raw	Raw
	L3_220701_DH_3197_DA4h_S08.raw	Raw

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Publications

Readout of histone methylation by Trim24 locally restricts chromatin opening by p53.

Isbel Luke L Iskar Murat M Durdu Sevi S Weiss Joscha J Grand Ralph S RS Hietter-Pfeiffer Eric E Kozicka Zuzanna Z Michael Alicia K AK Burger Lukas L Thomä Nicolas H NH Schübeler Dirk D

Nature structural & molecular biology 20230629 7

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 ...[more]

PMID: 37386214

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