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  The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine

Etchegaray, J. P., Chavez, L., Huang, Y., Ross, K. N., Choi, J., Martinez-Pastor, B., et al. (2015). The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine. Nature Cell Biology, 17(5), 545-557. doi:10.1038/ncb3147.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-3AD8-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-FA29-9
Genre: Journal Article

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 Creators:
Etchegaray, J. P., Author
Chavez, L., Author
Huang, Y., Author
Ross, K. N., Author
Choi, J., Author
Martinez-Pastor, B., Author
Walsh, R. M., Author
Sommer, C. A., Author
Lienhard, M.1, 2, Author              
Gladden, A., Author
Kugel, S., Author
Silberman, D. M., Author
Ramaswamy, S., Author
Mostoslavsky, G., Author
Hochedlinger, K., Author
Goren, A., Author
Rao, A., Author
Mostoslavsky, R., Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385701              
2La Jolla Institute for Allergy and Immunology, Sanford Consortium for Regenerative Medicine, UCSD , ou_persistent22              

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Free keywords: Acetylation Animals Cell Differentiation Cell Lineage Cells, Cultured Chromatin Assembly and Disassembly Cytosine/*analogs & derivatives/metabolism DNA-Binding Proteins/genetics/*metabolism Embryonic Stem Cells/*enzymology/pathology/transplantation Gene Expression Regulation, Developmental Genotype Histones/metabolism Homeodomain Proteins/genetics/metabolism Humans Induced Pluripotent Stem Cells/enzymology Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Mice, SCID Neurogenesis Octamer Transcription Factor-3/genetics/metabolism Phenotype Proto-Oncogene Proteins/genetics/*metabolism RNA Interference SOXB1 Transcription Factors/genetics/metabolism Signal Transduction Sirtuins/deficiency/genetics/*metabolism Teratoma/enzymology/pathology Transfection
 Abstract: How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC.

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Language(s): eng - English
 Dates: 2015-04-272015-05
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/ncb3147
ISSN: 1476-4679 (Electronic)1465-7392 (Print)
 Degree: -

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Title: Nature Cell Biology
  Other : Nat Cell Biol
Source Genre: Journal
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Publ. Info: London : Macmillan Magazines Ltd.
Pages: - Volume / Issue: 17 (5) Sequence Number: - Start / End Page: 545 - 557 Identifier: ISSN: 1465-7392
CoNE: https://pure.mpg.de/cone/journals/resource/954925625310