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

Kasem Kulkeaw, Tomoko Inoue, Tadafumi Iino, Kenzaburo Tani, Koichi Akashi, Nancy A. Speck, Yoichi Nakanishi, Daisuke Sugiyama

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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-Kit1CD311CD341 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 Twist12/2 relative to wild-type embryos. Microarray analysis and real-time polymerase chain reaction showed downregulated expression of Myb and Gata2 transcripts in Twist12/2 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.

元の言語英語
ページ(範囲)1672-1681
ページ数10
ジャーナルBlood Advances
1
発行部数20
DOI
出版物ステータス出版済み - 9 12 2017

All Science Journal Classification (ASJC) codes

  • Hematology

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