Dynamic long-range chromatin interactions control Myb proto-oncogene transcription during erythroid development

The key hematopoietic regulator Myb is essential to coordinate proliferation and differentiation. ChIP-Sequencing and 3C-Sequencing were used to characterize the structural and protein-binding dynamics of the Myb locus during erythroid differentiation. In proliferating cells expressing Myb, enhancers within the Myb-Hbs1l intergenic region were shown to form an active chromatin hub (ACH) containing the Myb promoter and first intron. Upon erythroid differentiation, Myb expression is downregulated and the ACH destabilized. A model is proposed for Myb activation by distal enhancers dynamically bound by KLF1 and the GATA1/TAL1/LDB1-complex, which primarily function as a transcription elongation element through chromatin looping.