|
|
GEO help: Mouse over screen elements for information. |
|
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)
|
|
Relations |
BioProject |
PRJNA286850 |
SRA |
SRP059418 |
Supplementary file |
Size |
Download |
File type/resource |
GSE69809_RAW.tar |
7.7 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
|