Cohesin links inflammation and cancer

Cohesin and CTCF are major players in 3D genome organisation. Nevertheless, loss of either cohesin or CTCF appear to have limited impact on transcriptional control, chromatin marks, or enhancer states in the experimental systems described to date. Our analysis shows that cohesin facilitates the dynamic regulation of gene transcription, enhancer states, and eRNA transcription in primary macrophages. The data are relevant for understanding the role of cohesin in transitions between transcriptional states, and have implications for recurrent cohesin mutations in cancer, in particular acute myeloid leukaemia. Many inducible macrophage genes are pro-inflammatory, and inflammatory signals are known to regulate the balance between self-renewal and differentiation of haematopietic stem and progenitor cells. Control of inflammatory gene expression provides a mechanistic link between cohesin and myeloid differentiation. Consistent with this idea, cohesin mutations are associated with reduced inflammatory gene expression in haematopietic stem and progenitor cells and in primary human acute myeloid leukaemia.