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Series GSE69809 Query DataSets for GSE69809
Status Public on Apr 04, 2016
Title Silencing of pericentric heterochromatin associated with SIRT6-dependent H3K18 deacetylation protects against mitotic errors and cellular senescence
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Pericentric heterochromatin silencing at mammalian centromeres is essential for mitotic fidelity and genomic stability. Defective pericentric silencing is observed in senescent cells, aging tissues, and mammalian tumors, but the underlying mechanisms and functional consequences of these defects are unclear. Here, we uncover a pivotal role of the human SIRT6 enzyme in pericentric transcriptional silencing, and this function protects against mitotic defects, genomic instability, and cellular senescence. At pericentric heterochromatin, SIRT6 promotes deacetylation of a new substrate, histone H3 lysine K18 (H3K18), and inactivation of SIRT6 in cells leads to H3K18 hyperacetylation and aberrant accumulation of pericentric transcripts. Strikingly, RNAi-depletion of these transcripts rescues the mitotic and senescence phenotypes of SIRT6-deficient cells. Together, our findings reveal a new function for SIRT6 and H3K18Ac regulation at heterochromatin, and demonstrate the pathogenic role of de-regulated pericentric transcription in aging- and cancer- related cellular dysfunction.
 
Overall design H3K18ac, H3K9ac, H3K9me3, H3K56ac and Input ChIP-seq for U2OS cell
 
Contributor(s) Xi Y, Tasselli L
Citation(s) 27043296
Submission date Jun 12, 2015
Last update date Aug 26, 2019
Contact name Yuanxin Xi
E-mail(s) xiyuanxin@yahoo.com
Phone 530-220-2067
Organization name The University of Texas MD Anderson Cancer Center
Department Bioinformatics and Computational Biology
Street address 1400 Pressler St
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (14)
GSM1709274 H3K18ac.Control_rep1
GSM1709275 H3K18ac.Control_rep2
GSM1709276 H3K18ac.SIRT6KD_rep1
Relations
BioProject PRJNA286850
SRA SRP059418

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
GSE69809_RAW.tar 7.7 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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