Cohesin is a protein complex that regulates gene expression and chromatin folding. The mutation of cohesin causes various human diseases including Cornelia de Lange syndrome (CdLS, a developmental disorder that affects many parts of the body) and cancer. Cohesin has various functions to regulate gene expression. For example, cohesin can mediate “chromatin loops” from an enhancer (a short genomic region that can activate gene transcription) to a promoter (a genomic region that can initiate gene transcription). This model suggests cohesin’s positive role on gene expression. However, the function of cohesin may be more varied than proposed so far, depending on the binding genomic positions.
In this study, Jiankang Wang, a Ph.D. student, and Dr. Ryuichiro Nakato, a lecturer at the Institute for Quantitative Biosciences (IQB), the University of Tokyo, conducted a large-scale analysis to identify the unclarified functions of cohesin, especially bound on “intragenic” region, in collaboration with Drs. Masashige Bando and Katsuhiko Shirahige at IQB. They generated a large-sale data including ChIP-seq (a method to analyze protein interactions with DNA), RNA-seq (a method to quantify gene expression level) and Hi-C (a method to capture chromatin structure) and analyzed them using a machine-learning approach. They identified intragenic cohesin sites that were negatively correlated with gene expression. The special intragenic cohesin sites (defined as “DICs”) can be observed in various types of cells, including cells from patients with CdLS. The findings from genome-wide analysis suggest an additional role for cohesin in the regulation of gene expression, which may be correlated with the phenotype of CdLS.

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