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H3.3 phosphorylation promotes enhancer acetylation and lineage specification

ABSTRACT: H3.3 phosphorylation promotes enhancer acetylation and lineage specification

PROVIDER: PRJNA471713 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7172880_1.fastq.gz	Fastqsanger.gz
	SRR7172880_2.fastq.gz	Fastqsanger.gz
	SRR7172890_1.fastq.gz	Fastqsanger.gz
	SRR7172890_2.fastq.gz	Fastqsanger.gz
	SRR7172900_1.fastq.gz	Fastqsanger.gz

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H3.3 phosphorylation promotes enhancer acetylation and lineage specification [RNA-seq]

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H3.3 phosphorylation promotes enhancer acetylation and lineage specification [ATAC-seq]

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H3.3 phosphorylation promotes enhancer acetylation and lineage specification

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Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation.

Project description:The histone variant H3.3 is enriched at enhancers and active genes, as well as repeat regions such as telomeres and retroelements, in mouse embryonic stem cells (mESCs)1-3. Although recent studies demonstrate a role for H3.3 and its chaperones in establishing heterochromatin at repeat regions4-8, the function of H3.3 in transcription regulation has been less clear9-16. Here, we find that H3.3-specific phosphorylation17-19 stimulates activity of the acetyltransferase p300 in trans, suggesting that H3.3 acts as a nucleosomal cofactor for p300. Depletion of H3.3 from mESCs reduces acetylation on histone H3 at lysine 27 (H3K27ac) at enhancers. Compared with wild-type cells, those lacking H3.3 demonstrate reduced capacity to acetylate enhancers that are activated upon differentiation, along with reduced ability to reprogram cell fate. Our study demonstrates that a single amino acid in a histone variant can integrate signaling information and impact genome regulation globally, which may help to better understand how mutations in these proteins contribute to human cancers20,21.

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Project description:The re-assembly of chromatin following DNA replication is a critical event in the maintenance of genome integrity. Histone H3 acetylation at K56 and phosphorylation at T45 are two important chromatin modifications that accompany chromatin assembly. Here we report a microarray expression study of the protein kinase Pkc1, histone acetyl transferase Rtt109 and histone H3 in Saccharomyces cerevisiae under conditions of replicative stress.

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