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RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element
Author(s) -
Levantini Elena,
Lee Sanghoon,
Radomska Hanna S,
Hetherington Christopher J,
AlberichJorda Meritxell,
Amabile Giovanni,
Zhang Pu,
Gonzalez David A,
Zhang Junyan,
Basseres Daniela S,
Wilson Nicola K,
Koschmieder Steffen,
Huang Gang,
Zhang DongEr,
Ebralidze Alexander K,
Bonifer Constanze,
Okuno Yutaka,
Gottgens Bertie,
Tenen Daniel G
Publication year - 2011
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.2011.285
Subject(s) - biology , haematopoiesis , runx1 , stem cell , microbiology and biotechnology , cd34 , gene , regulation of gene expression , genetics
The transcription factor RUNX1 is essential to establish the haematopoietic gene expression programme; however, the mechanism of how it activates transcription of haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel insights into RUNX1 function by studying regulation of the human CD34 gene, which is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs, we identified a novel downstream regulatory element (DRE), which is bound by RUNX1 and is necessary for human CD34 expression in long‐term (LT)‐HSCs. Conditional deletion of Runx1 in mice harbouring human CD34 promoter–DRE constructs abrogates human CD34 expression. We demonstrate by chromosome conformation capture assays in LT‐HSCs that the DRE physically interacts with the human CD34 promoter. Targeted mutagenesis of RUNX binding sites leads to perturbation of this interaction and decreased human CD34 expression in LT‐HSCs. Overall, our in vivo data provide novel evidence about the role of RUNX1 in mediating interactions between distal and proximal elements of the HSC gene CD34 .