Aditi, Majumder and Khaja Mohieddin , Syed and Sunu , Joseph and Debasree, Dutta (2015) Histone Chaperone HIRA in Regulation of Transcription Factor RUNX1. J Biol Chem, 290 (21). pp. 13053-13063. ISSN 0146-5015

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Abstract

RUNX1 (Runt-related transcription factor 1) is indispensable for the generation of hemogenic endothelium. However, the regulation of RUNX1 during this developmental process is poorly understood. We investigated the role of the histone chaperone HIRA (histone cell cycle regulation-defective homolog A) from this perspective and report that HIRA significantly contributes toward the regulation of RUNX1 in the transition of differentiating mouse embryonic stem cells from hemogenic to hematopoietic stage. Direct interaction of HIRA and RUNX1 activates the downstream targets of RUNX1 implicated in generation of hematopoietic stem cells. At the molecular level, HIRA-mediated incorporation of histone H3.3 variant within the Runx1 +24 mouse conserved noncoding element is essential for the expression of Runx1 during endothelial to hematopoietic transition. An inactive chromatin at the intronic enhancer of Runx1 in absence of HIRA significantly repressed the transition of cells from hemogenic to hematopoietic fate. We expect that the HIRA-RUNX1 axis might open up a novel approach in understanding leukemogenesis in future.

Item Type:	Article
Uncontrolled Keywords:	hematopoiesis, hematopoietic stem cells, histone, histone chaperone, transcription factor, H3.3 variant, hematopoietic precursor
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	27 Dec 2016 04:01
Last Modified:	27 Dec 2016 06:35
URI:	http://rgcb.sciencecentral.in/id/eprint/68

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