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Series GSE65836 Query DataSets for GSE65836
Status Public on Mar 12, 2015
Title The Histone Deacetylase Sirt6 Controls Embryonic Stem Cell Fate Via Tet-Mediated Production of 5-Hydroxymethylcytosine
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary How embryonic stem cells (ESC) commit to specific cell lineages and ultimately 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 two categories of epigenetic changes are not understood. Here we demonstrate the hierarchical interplay between the histone deacetylase, sirtuin 6 (Sirt6), which targets acetylated histone H3 at lysines 9 and 56 (H3K9ac and H3K56ac), and the Tet (Ten-eleven translocation) enzymes, which convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knocSirt6 KOut (S6Sirt6 KO) mice are skewed towards neuroectoderm development. This phenotype is associated with derepression of Oct4, Sox2 and Nanog, which in turn causes an upregulation of Tet enzymes and elevated production of 5hmC. Genome-wide analysis revealed an upregulation of neuroectoderm genes marked with 5hmC in S6Sirt6 KO ESCs, thereby implicating Tet enzymes in the neuroectoderm-skewed differentiation phenotype of S6Sirt6 KO ESCs, which is fully rescued upon knockdown of Tets. We demonstrate a new role for Sirt6 as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-dependent regulation of 5hmC levels.
Overall design ChIP-Seq experiments to examine two different histone modifications (H3K9ac and H3K56ac) and Sirt6 binding in Sirt6 wild type (WT) and knock-out (Sirt6 KO) mouse embryonic stem cells with and without treatment using differentiating agent retonic acid (RA).
CMS-IP 5-Hydroxymethylation mapping in wild type (WT, 129 mouse strain) and Sirt6 knockout (S6KO, 129 mouse strain) mouse embryonic stem cells.
Contributor(s) Etchegaray J, Mostoslavsky R, Goren A, Ross KN
Citation(s) 25915124
Submission date Feb 10, 2015
Last update date May 15, 2019
Contact name Kenneth N Ross
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Street address 450 Brookline Ave., Rm M640
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (17)
GSM1401409 S6KO CMS-IP
GSM1401410 S6KO Input
GSM1401411 WT CMS-IP
BioProject PRJNA275163
SRA SRP054052

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65836_MEDIPS_ko_vs_wt.txt.gz 171.0 Kb (ftp)(http) TXT
GSE65836_RAW.tar 2.7 Gb (http)(custom) TAR (of TDF, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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