U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX1057275: GSM1709278: H3K56ac.Control; Homo sapiens; ChIP-Seq
1 ILLUMINA (Illumina HiSeq 2000) run: 65.7M spots, 13.3G bases, 8.2Gb downloads

Submitted by: Gene Expression Omnibus (GEO)
Study: Silencing of pericentric heterochromatin associated with SIRT6-dependent H3K18 deacetylation protects against mitotic errors and cellular senescence
show Abstracthide Abstract
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
Sample: H3K56ac.Control
SAMN03771150 • SRS959691 • All experiments • All runs
Organism: Homo sapiens
Library:
Instrument: Illumina HiSeq 2000
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: Cells were fixed with 1% formaldehyde for 8 min, quenched with 1.25 M glycine, washed in PBS. Cells were resuspended in cells lysis buffer (50 mM Tris pH 8.0, 10 mM EDTA, 1% SDS, 1x Roche Complete Protease inhibitor), kept in ice for 10 min, and sonicated using Bioruptor. Following sonication insoluble material was pelleted by centrifugation at 16000g for 10 minutes at 4°C. A small sample of soluble crosslinked chromatin was purified, checked for correct sonication size range. 25 ug of chromatin was diluted to 350ul with RIPA buffer (10 mM Tris pH 7.5, 140 mM NaCl, 1mM EDTA, 0.5 mM EGTA, 1% Triton, 0.1% SDS, 0.1% sodium deoxycholate, 1x Roche Complete Protease inhibitor). 10 μl of Protein A Dynabeads (Invitrogen) prebound with 2 μg of histone marks antibodies were added. Samples were incubated overnight at 4°C with rotation. Beads were precipitated on magnet stand and washed 3 times with 1 mL of RIPA buffer and once with TE. Crosslink was reversed with 250 μl of elution buffer (20 mM Tris pH 7.5, 5 mM EDTA, 50 mM NaCl, 1% SDS, 5 μg/mL proteinase K) at 65°C for 2 hours. DNA was purified with Qiagen PCR cleanup kit. Concentration of eluted chromatin was measured with Qubit dsDNA HS Assay Kit (Life Technology). Sequencing libraries were prepared using the Illumina TruSeq DNA Sample Preparation Kit according to the manufacturer's protocol. After adapter ligation DNA was PCR amplified with Illumina primers for 15 cycles and library fragments of ~250-450 bp (insert plus adaptor) were band isolated from an agarose gel. DNA fragments were sequenced using paired-end sequencing technology on Illumina HiSeq 2000 platform.
Experiment attributes:
GEO Accession: GSM1709278
Links:
External link:
Runs: 1 run, 65.7M spots, 13.3G bases, 8.2Gb
Run# of Spots# of BasesSizePublished
SRR206134265,695,27313.3G8.2Gb2016-04-08

ID:
1534260

Supplemental Content

Search details

See more...

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...