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Dynamic long‐range chromatin interactions control Myb proto‐oncogene transcription during erythroid development
Author(s) -
Stadhouders Ralph,
Thongjuea Supat,
AndrieuSoler Charlotte,
Palstra RobertJan,
Bryne Jan Christian,
van den Heuvel Anita,
Stevens Mary,
de Boer Ernie,
Kockx Christel,
van der Sloot Antoine,
van den Hout Mirjam,
van IJcken Wilfred,
Eick Dirk,
Lenhard Boris,
Grosveld Frank,
Soler Eric
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.450
Subject(s) - biology , chromatin , enhancer , myb , transcription factor , microbiology and biotechnology , transcription (linguistics) , genetics , gene , linguistics , philosophy
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.