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Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation
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). While recent studies demonstrate a role for H3.3 and its chaperones in establishing heterochromatin at repeat regions(4–8), t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598431/ https://www.ncbi.nlm.nih.gov/pubmed/31152160 http://dx.doi.org/10.1038/s41588-019-0428-5 |
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author | Martire, Sara Gogate, Aishwarya A. Whitmill, Amanda Tafessu, Amanuel Nguyen, Jennifer Teng, Yu-Ching Tastemel, Melodi Banaszynski, Laura A. |
author_facet | Martire, Sara Gogate, Aishwarya A. Whitmill, Amanda Tafessu, Amanuel Nguyen, Jennifer Teng, Yu-Ching Tastemel, Melodi Banaszynski, Laura A. |
author_sort | Martire, Sara |
collection | PubMed |
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). While recent studies demonstrate a role for H3.3 and its chaperones in establishing heterochromatin at repeat regions(4–8), the function of H3.3 in transcription regulation has been less clear(9–16). Here, we find that H3.3-specific phosphorylation(17–19) 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. Cells 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 globally impact genome regulation, which may help better understand how mutations in these proteins contribute to human cancers(20,21). |
format | Online Article Text |
id | pubmed-6598431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-65984312019-11-30 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 A. Nat Genet Article 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). While recent studies demonstrate a role for H3.3 and its chaperones in establishing heterochromatin at repeat regions(4–8), the function of H3.3 in transcription regulation has been less clear(9–16). Here, we find that H3.3-specific phosphorylation(17–19) 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. Cells 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 globally impact genome regulation, which may help better understand how mutations in these proteins contribute to human cancers(20,21). 2019-05-31 2019-06 /pmc/articles/PMC6598431/ /pubmed/31152160 http://dx.doi.org/10.1038/s41588-019-0428-5 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Martire, Sara Gogate, Aishwarya A. Whitmill, Amanda Tafessu, Amanuel Nguyen, Jennifer Teng, Yu-Ching Tastemel, Melodi Banaszynski, Laura A. Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation |
title | Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation |
title_full | Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation |
title_fullStr | Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation |
title_full_unstemmed | Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation |
title_short | Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation |
title_sort | phosphorylation of histone h3.3 at serine 31 promotes p300 activity and enhancer acetylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598431/ https://www.ncbi.nlm.nih.gov/pubmed/31152160 http://dx.doi.org/10.1038/s41588-019-0428-5 |
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