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Series GSE81403 Query DataSets for GSE81403
Status Public on Jun 30, 2017
Title Convergent roles of ATF3 and CSL in chromatin control of CAF activation [ATF3 ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cancer associated fibroblasts (CAFs) play an important role in initiating and promoting epithelial cancers. The specific chromatin modifications involved in CAF activation remain to be elucidated. CSL, a constitutive transcriptional repressor and mediator of canonical Notch signaling, functions as a direct negative regulator of CAF effector genes and suppresses cancer/stromal cell expansion. We find that ATF3, a key stress responsive transcriptional repressor up-regulated in the acute UVA response of skin fibroblasts, is down-modulated in stromal cells of premalignant skin SCC lesions similarly to CSL. Increased ATF3 expression counteracts the consequences of compromised CSL, binding to a large set of overlapping target genes. At low basal levels, ATF3 converges with CSL in negative control of CAF activation, binding to a very small number of genomic loci that encompass mostly non-coding RNAs and pseudogenes. Silencing of ATF3 results in chromatin modifications and Pol II recruitment to many loci to which ATF3 does not bind, which are similarly affected by CSL silencing. The observed changes are of functional significance, as Bet inhibitors, which unlink activated chromatin from the basic transcription apparatus, have opposite effects of ATF3 or CSL silencing on all tested CAF effector genes. They exert a similar impact on clinically-derived CAFs both in vitro and upon topical in vivo treatment. Thus, ATF3 converges with CSL in global chromatin control of CAF activation with their loss eliciting epigenetic changes amenable to cancer and stroma-focused intervention.
 
Overall design Examination of genome-wide over-expressed ATF3 binding sites in primary human dermal fibroblasts
 
Contributor(s) Kim DE, Angelino P, Dotto G
Citation(s) 28684431
Submission date May 13, 2016
Last update date May 15, 2019
Contact name Paolo Angelino
E-mail(s) paolo.angelino@isb-sib.ch
Organization name SIB Swiss Institute of Bioinformatics
Department BCF
Street address Quartier Sorge, Bâtiment Génopode
City Lausanne
ZIP/Postal code 1015
Country Switzerland
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (4)
GSM2151902 endogenus ATF3 ChIPSeq [DEK007]
GSM2151903 Input DNA [DEK008]
GSM2151904 overexpressed ATF3 ChIPSeq [DEK009]
This SubSeries is part of SuperSeries:
GSE81406 Convergent roles of ATF3 and CSL in chromatin control of CAF activation
Relations
BioProject PRJNA321475
SRA SRP075008

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Supplementary file Size Download File type/resource
GSE81403_pics_dek007-dek008_peaks.bed.gz 2.2 Kb (ftp)(http) BED
GSE81403_pics_dek009-dek010_peaks.bed.gz 285.4 Kb (ftp)(http) BED
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Raw data are available in SRA
Processed data are available on Series record

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