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

Sara Martire, Aishwarya A. Gogate, Amanda Whitmill, Amanuel Tafessu, Jennifer Nguyen, Yu Ching Teng, Melodi Tastemel, Laura Banaszynski

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)941-946
Number of pages6
JournalNature genetics
Volume51
Issue number6
DOIs
StatePublished - Jun 1 2019

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Acetylation
Histones
Serine
Phosphorylation
Retroelements
Heterochromatin
Telomere
Lysine
Genome
Amino Acids
Mutation
Genes
Proteins
Mouse Embryonic Stem Cells

ASJC Scopus subject areas

  • Genetics

Cite this

Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation. / Martire, Sara; Gogate, Aishwarya A.; Whitmill, Amanda; Tafessu, Amanuel; Nguyen, Jennifer; Teng, Yu Ching; Tastemel, Melodi; Banaszynski, Laura.

In: Nature genetics, Vol. 51, No. 6, 01.06.2019, p. 941-946.

Research output: Contribution to journalArticle

Martire, S, Gogate, AA, Whitmill, A, Tafessu, A, Nguyen, J, Teng, YC, Tastemel, M & Banaszynski, L 2019, 'Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation', Nature genetics, vol. 51, no. 6, pp. 941-946. https://doi.org/10.1038/s41588-019-0428-5
Martire S, Gogate AA, Whitmill A, Tafessu A, Nguyen J, Teng YC et al. Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation. Nature genetics. 2019 Jun 1;51(6):941-946. https://doi.org/10.1038/s41588-019-0428-5
Martire, Sara ; Gogate, Aishwarya A. ; Whitmill, Amanda ; Tafessu, Amanuel ; Nguyen, Jennifer ; Teng, Yu Ching ; Tastemel, Melodi ; Banaszynski, Laura. / Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation. In: Nature genetics. 2019 ; Vol. 51, No. 6. pp. 941-946.
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