The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues.
Bottom Line: 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.We could not detect significant changes in the chromatin contacts at the Pcdh locus when comparing brains from wild-type and SA1 embryos.Given the role of Reg proteins in inflammation, such reduction may contribute to the increased incidence of pancreatic cancer observed in these animals.
Affiliation: Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.Show MeSH
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Mentions: We next analysed cohesin distribution around the transcription start site (TSS) of the genes that are expressed specifically in each tissue. To assess tissue-specific gene expression RNA-seq was performed in the same samples used for ChIP (Supplementary Tables S2 and S3). We defined tissue-specific genes as those differentially expressed when compared with the other tissue (log2FC > 4, FDR < 0.05), in which the expression should be low, i.e. Fragments Per Kilobase of exon per Million fragments mapped (FPKM) <3. Using these criteria, we selected 2126 cortex-specific genes and 514 pancreas-specific genes. Gene ontology analyses verified the functional specificity of the gene sets (Figure 2A and Supplementary Table S4). We found that cohesin binding sites (both SMC1 and SA1) are enriched around the TSS of tissue-specific genes mainly in the tissue in which they are expressed (Figure 2B).
Affiliation: Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.