MEAF6 is essential for cell proliferation and plays a role in the assembly of KAT7 complexes

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 homologs has not been elucidated in any species. Here we revealed the role of Meaf6 utilizing inducible Meaf6 KO ES cells. By elimination of Meaf6, proliferation ceased although histone acetylations were largely unaffected. In the absence of Meaf6, one of the Myst family members Myst2/Kat7 increased the ability to interact with PHD-finger proteins. This study is the first indication of the function of Meaf6, which shows it is not essential for HAT activity but modulates the assembly of the Kat7 complex.

MYST家族基因编码赖氨酸乙酰转移酶（lysine acetyltransferases），主要通过介导组蛋白乙酰化修饰，调控转录、DNA复制与DNA损伤应答过程。该类酶与PHD指蛋白（PHD-finger proteins，Brpf或Jade家族蛋白）以及小型非催化亚基Ing4/5和Meaf6共同组装形成四聚体复合物。尽管该复合物的所有组分从酵母到哺乳动物均高度保守，但Meaf6及其同源蛋白在任何物种中的功能均未被阐明。本研究借助诱导型Meaf6敲除（Knockout，KO）胚胎干细胞（ES cells），揭示了Meaf6的生物学功能：敲除Meaf6后，细胞增殖停滞，但组蛋白乙酰化水平整体未受显著影响；当缺失Meaf6时，MYST家族成员之一Myst2/Kat7与PHD指蛋白的相互作用能力显著增强。本研究首次揭示了Meaf6的功能，其并非组蛋白乙酰转移酶（Histone Acetyltransferase，HAT）活性所必需，而是通过调控Kat7复合物的组装发挥作用。