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

Ralph Stadhouders, S Thongjuea, C Andrieu-Soler, Robert-jan Palstra, JC Bryne, anita Heuvel, M (Martijn) Stevens, Ernie Boer, Christel Kockx, A van der Sloot, M van den Hout, Wilfred van Ijcken, D Eick, B Lenhard, Frank Grosveld, Eric Soler

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103 Citations (Scopus)

Abstract

The key haematopoietic regulator Myb is essential for coordinating proliferation and differentiation. ChIP-Sequencing and Chromosome Conformation Capture (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. This first intron was found to harbour the transition site from transcription initiation to elongation, which takes place around a conserved CTCF site. Upon erythroid differentiation, Myb expression is downregulated and the ACH destabilized. We propose a model 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. The EMBO Journal (2012) 31, 986-999. doi: 10.1038/emboj.2011.450; Published online 13 December 2011
Original languageUndefined/Unknown
Pages (from-to)986-999
Number of pages14
JournalEMBO Journal
Volume31
Issue number4
DOIs
Publication statusPublished - 2012

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