The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues

Nucleic Acids Research
Ana CuadradoAna Losada

Abstract

Cohesin, which in somatic vertebrate cells consists of SMC1, SMC3, RAD21 and either SA1 or SA2, mediates higher-order chromatin organization. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these show reduced overlap with CCCTC-binding factor (CTCF) and are enriched at the regulatory regions of tissue-specific genes. Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1. Analyses of chromatin contacts at the Protocadherin (Pcdh) and Regenerating islet-derived (Reg) gene clusters, mostly expressed in brain and pancreas, respectively, revealed remarkable differences that correlate with the presence of cohesin. We could not detect significant changes in the chromatin contacts at the Pcdh locus when comparing brains from wild-type and SA1 null embryos. In contrast, reduced dosage of SA1 altered the architecture of the Reg locus and decreased the expression of Reg genes in the pancreas of SA1 heterozygous mice. Given the role of Reg pr...Continue Reading

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Methods Mentioned

BETA
immunoprecipitation
PCR
ChIP-seq
Feature Extraction
RNA-seq
ChIP
Hi-C

Software Mentioned

Limma
Ensembl
FastQC
FatiScan
ChromHMM
Fastq
BEDTools
4Cseqpipe
Samtools
TopHat

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