Genomics

Dataset Information

29

CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops


ABSTRACT: Background: Recent genome-wide association studies (GWAS) have identified more than 100 loci associated with increased risk of prostate cancer, most of which are in non-coding regions of the genome. Understanding the function of these non-coding risk loci is critical to elucidate the genetic susceptibility to prostate cancer. Results: We generated genome-wide regulatory element maps and performed genome-wide chromosome confirmation capture assays (in situ Hi-C) in normal and tumorigenic prostate cells. Using this information, we annotated the regulatory potential of 2,181 fine-mapped PCa risk-associated SNPs and predicted a set of target genes that are regulated by PCa risk-related H3K27Ac-mediated loops. We next identified PCa risk-associated CTCF sites involved in long-range chromatin loops. We used CRISPR-mediated deletion to remove PCa risk-associated CTCF anchor regions and the CTCF anchor regions looped to the PCa risk-associated CTCF sites; we observed up to 100 fold increases in expression of genes within the loops when the PCa risk-associated CTCF anchor regions were deleted. Conclusions: We have identified GWAS risk loci involved in long-range loops that function to repress gene expression within chromatin loops. Our studies provide new insights into the genetic susceptibility to prostate cancer. Overall design: ChIP-seq, RNA-seq, Hi-C in prostate cells.

REANALYSIS of: GSE98898

INSTRUMENT(S): Illumina Genome Analyzer (Homo sapiens)

ORGANISM(S): Homo sapiens  

SUBMITTER: Yu (Phoebe) Guo  

PROVIDER: GSE118514 | GEO | 2018-08-15

REPOSITORIES: GEO

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Publications

CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops.

Guo Yu Y   Perez Andrew A AA   Hazelett Dennis J DJ   Coetzee Gerhard A GA   Rhie Suhn Kyong SK   Farnham Peggy J PJ  

Genome biology 20181008 1


BACKGROUND:Recent genome-wide association studies (GWAS) have identified more than 100 loci associated with increased risk of prostate cancer, most of which are in non-coding regions of the genome. Understanding the function of these non-coding risk loci is critical to elucidate the genetic susceptibility to prostate cancer. RESULTS:We generate genome-wide regulatory element maps and performed genome-wide chromosome confirmation capture assays (in situ Hi-C) in normal and tumorigenic prostate ce  ...[more]

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