Investigation of molecular mechanism governing open chromatin formation in mouse ES cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03687
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kumamoto University
• Principal Investigator: Niwa Hitoshi 熊本大学, 発生医学研究所, 教授 (80253730)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: エピジェネティクス / ヒストン / アセチル化

Outline of Final Research Achievements

Myst family genes encode lysine acetyltransferases that mainly mediate histone acetylation to control transcription, DNA replication and DNA damage response. They form tetrameric complexes with PHD-finger proteins (Brpfs or Jades) and small non-catalytic subunits Ing4/5 and Meaf6. Although all the components of the complex are well-conserved from yeast to mammals, the function of Meaf6 and its homolog has not been elucidated in any species. Here we revealed the role of Meaf6 in the Myst complex utilizing inducible Meaf6 KO ES cells. Elimination of Meaf6 results in cease of proliferation although histone acetylation is largely unaffected. In the absence of Meaf6, one of the Myst family members Myst2 increased its ability to interact with PHD-finger proteins. This is the first indication of the function of Meaf6, which is not essential for HAT activity, but modulates the stoichiometry of the Myst complex.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

Meaf6と他の遺伝子の融合遺伝子が、子宮内膜間質肉腫において見出されており、そのい癌遺伝子としての機能が推定されている。我々の研究は、Meaf6が細胞増殖制御に関わることを初めて明らかにしたものであり、今後の発がんとの関連性の解明に資するものである。