GSE177045
Large-scale multi-omics analysis suggests an important role of intragenic cohesin in tissue-specific transcription.
Cohesin is a protein complex that is essential for chromosome segregation. Cohesin regulates gene expression by insulation and chromatin domain formation with insulation factor CTCF. It was also reported that CTCF-independent cohesin-binding sites co-localize with transcription factors (TFs) for enhancer-promoter interaction. However, it is not a trivial task to assign whole-genome cohesin-binding regions into various functions. Also, the context-specific roles of cohesin-mediated interactions, especially on intragenic region, remains unsolved. To this end, we performed a comprehensive characterization of DNA-binding sites for cohesin and transcription factors (TFs) in MCF-7 cells with and without transcription stimulus. We integrated these epigenomic data with transcriptomic and chromatin interactions data to analyze context-specific cohesin function in genome-wide manner. As a result, we extracted a new subset of cohesin-binding sites named decreased intragenic cohesin sites (DICs), which were different from previous known functions of cohesin. DICs were negatively correlated with transcriptional regulation: a part of them were related to enhancer markers and “paused” RNA polymerase 2, while others contributed to chromatin architectures. The intron enriched DICs also showed chromatin de-compaction and special genomic bindings. Further conventional machine learning approach also captured similar DICs with distinguishable features. More importantly, DICs could be found in various tissues and cell lines, including cohesinopathy patient cells, to play a role in the disturbed transcription. These results suggested a novel function of cohesin on intragenic regions for gene transcription regulation. Overall design: ChIP-seq and RNA-seq in MCF-7, RPE, Fibrolast and other cell lines