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Series GSE36616 Query DataSets for GSE36616
Status Public on Sep 09, 2013
Title Lamin B1 depletion in senescent cells triggers large-Scale changes in gene expression and in the chromatin landscape[ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cellular senescence is a stable proliferation arrest in response to stress, associated with an altered secretory pathway (Senescence Associated Secretory Phenotype (SASP)). Senescence-associated proliferation arrest and the SASP are thought to act in concert to promote tumor suppression and tissue aging. While chromatin regulation and down regulation of lamin B1 have been implicated as effectors of cell senescence, functional interactions between them are poorly understood. We compared the genome-wide distributions of H3K4me3 and H3K27me3 between proliferating and senescent primary human cells and found dramatic differences, including large-scale domains of H3K4me3- and H3K27me3-enriched "mesas" and H3K27me3-depleted "canyons" in senescent cells. Senescent mesas form at the sites of lamin B1-associated domains (LADs) in proliferating cells. Mesas also overlap with regions that exhibit DNA hypomethylation in cancer, suggesting that chromatin changes in pre-malignant senescent cells foreshadow epigenetic changes in cancer. Proliferating fibroblasts from Hutchinson-Gilford Progeria Syndrome patients expressing mutant lamin A (progerin) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence and tissue aging. In contrast, canyons form mostly in between LADs and are enriched in genes, gene promoters and enhancers. Strikingly, H3K27me3 loss in canyons is correlated with upregulation of key senescence genes, including genes comprising the SASP, indicating a link between global changes in chromatin structure and local regulation of gene expression. Finally, premature reduction of lamin B1 in midlife proliferating cells triggers formation of senescence-associated mesas and canyons and accelerated senescence. Together, our data illustrate a profound reorganization of chromatin during senescence, and suggest that down regulation of lamin B1 in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging and cancer.
Overall design One lane per sample, with replicates; four lanes H3 (one proliferating, one senescent, one control, one Ras-induced), four lanes H3K27me3 (three proliferating, one senescent), two lanes H3K4me3 (one control, one ras-induced)
Contributor(s) Shah PP, Donahue G, Otte G, Capell B, Nelson DM, Cao K, Aggarwala V, Cruickshanks H, Rai TS, McBryan T, Gregory B, Sandhu D, Adams PD, Berger SL
Citation(s) 23934658
Submission date Mar 19, 2012
Last update date May 15, 2019
Contact name Gregory Donahue
Organization name The University of Pennsylvania
Department Cell & Developmental Biology
Lab Zaret Lab
Street address 3400 Civic Center Blvd, Bldg 421
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (17)
GSM897555 Proliferating Histone 3 ChIP
GSM897556 Proliferating H3K4me3 ChIP
GSM897557 Proliferating H3K27me3 ChIP R1
This SubSeries is part of SuperSeries:
GSE36641 Lamin B1 depletion in senescent cells leads to large-scale changes in the chromatin landscape
SRA SRP011584
BioProject PRJNA155425

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Supplementary file Size Download File type/resource
GSE36616_H3K27me3_canyons.bed.gz 11.3 Kb (ftp)(http) BED
GSE36616_H3K27me3_mesas.bed.gz 11.9 Kb (ftp)(http) BED
GSE36616_H3K4me3_OIS_mesas.bed.gz 6.3 Kb (ftp)(http) BED
GSE36616_H3K4me3_mesas.bed.gz 5.1 Kb (ftp)(http) BED
GSE36616_LADs.bed.gz 14.2 Kb (ftp)(http) BED
GSE36616_RAW.tar 2.9 Gb (http)(custom) TAR (of BW)
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