Role of H3K36 methyltransferase Mmset in Hematopoietic stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19566
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Chiba University
• Principal Investigator: Mochizuki Makiko 千葉大学, 大学院医学研究院, 特任研究員 (40751300)
• Research Collaborator: IWAMA Atsushi ; URA Kiyoe
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Mmset / Whsc1 / Nsd1 / HSC / H3K36me2/3

Outline of Final Research Achievements

Wolf-Hirschhorn syndrome candidate 1 (WHSC1), also known as NSD2 or MMSET, functions as a one of the Histone H3 Lysin36 methyltransferase (H3K36me) transcriptional regulation together with developmental transcription factors and that the Whsc1 deficiency is responsible for WHS.
In this reserch, we showed that Whsc1 is required for normal Hematopoietic stem cell (HSC) homeostasis. We performed Hematopoietic analysis in both Whsc1 conventional knockout (KO) and conditional knockout (cKO) mice. HSC number was slightly increased in adult Whsc1 cKO. Nevertheless competitive reconstitution of hematopoietic cell analysis reveals that Whsc1-deficient HSCs impaired reconstitution capacity in vivo. These data indicate DNA damage repair associated modification H3K36me plays important role for HSC self-renewal, differentiation and reconstitution.

Free Research Field

血液学