title: Histone Chaperone HIRA in Regulation of Transcription Factor RUNX1.
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.
authors.affiliation: From the Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram, 695 014 Kerala, India and.
authors.forename: Aditi
authors.initials: A
authors.lastname: Majumder
authors.affiliation: From the Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram, 695 014 Kerala, India and.
authors.forename: Khaja Mohieddin
authors.initials: KM
authors.lastname: Syed
authors.affiliation: From the Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram, 695 014 Kerala, India and.
authors.forename: Sunu
authors.initials: S
authors.lastname: Joseph
authors.affiliation: the Institute of Child Health, University College of London, London WC1E 6BT, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scambler
authors.affiliation: From the Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram, 695 014 Kerala, India and debasreedutta@rgcb.res.in.
authors.forename: Debasree
authors.initials: D
authors.lastname: Dutta
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D056488:Histone Chaperones / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D050676:Core Binding Factor Alpha 2 Subunit; C484187:Hira protein, mouse; D056488:Histone Chaperones; D012333:RNA, Messenger; C493726:Runx1 protein, mouse; D014157:Transcription Factors
keywords: H3.3 variant; hematopoiesis; hematopoietic precursor; hematopoietic stem cells; histone; histone chaperone; transcription factor
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