Figure 3

Model for cohesin’s role in AML and other myeloid malignancies. Cohesin has an important function in the nucleus: it mediates chromosome interactions within topologically associated domains (TADs). Within TADs, cohesin connects conserved regulatory elements (CREs) with promoters, thereby regulating gene transcription. When cohesin function is compromised by a heterozygous mutation, as in AML, this leads to loss of CRE-promoter communication at specific hematopoietic genes, such as RUNX1. The result is dysregulation of hematopoietic transcription programs, which could facilitate the development of AML. In addition, loss of tissue-specific sub-domain structures affects the global hematopoietic transcription program.