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Twist1 regulates embryonic hematopoietic differentiation through binding to Myb and Gata2 promoter regions.


ABSTRACT: Mechanisms underlying differentiation of embryonic hematopoietic stem/progenitor cells (HSPCs) remain unclear. In mouse, intra-aortic clusters (IACs) form in the aorta-gonad-mesonephros region and acquire HSPC potential after 9.5 days postcoitum (dpc). In this study we demonstrate that Twist1 is highly expressed in c-Kit+CD31+CD34+ IACs, which are equivalent to embryonic HSPCs, compared with adult HSPCs. Progenitor activities of colony-forming unit (CFU) of granulocytes and macrophages, CFU of macrophages, burst-forming unit of erythroid, and B lymphopoiesis were impaired in IACs of Twist1-/- relative to wild-type embryos. Microarray analysis and real-time polymerase chain reaction showed downregulated expression of Myb and Gata2 transcripts in Twist1-/- IACs. Chromatin immunoprecipitation and promoter binding assays indicated that Twist1 directly binds the Myb and Gata2 promoters in 10.5-dpc IACs. We conclude that Twist1 is a novel transcriptional regulator of HSPC differentiation through direct binding to promoter regions of key regulators of the process.

SUBMITTER: Kulkeaw K 

PROVIDER: S-EPMC5728333 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Twist1 regulates embryonic hematopoietic differentiation through binding to <i>Myb</i> and <i>Gata2</i> promoter regions.

Kulkeaw Kasem K   Inoue Tomoko T   Iino Tadafumi T   Tani Kenzaburo K   Akashi Koichi K   Speck Nancy A NA   Nakanishi Yoichi Y   Sugiyama Daisuke D  

Blood advances 20170831 20


Mechanisms underlying differentiation of embryonic hematopoietic stem/progenitor cells (HSPCs) remain unclear. In mouse, intra-aortic clusters (IACs) form in the aorta-gonad-mesonephros region and acquire HSPC potential after 9.5 days postcoitum (dpc). In this study we demonstrate that Twist1 is highly expressed in c-Kit<sup>+</sup>CD31<sup>+</sup>CD34<sup>+</sup> IACs, which are equivalent to embryonic HSPCs, compared with adult HSPCs. Progenitor activities of colony-forming unit (CFU) of granu  ...[more]

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