論文

査読有り 国際誌
2017年9月20日

Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development.

Scientific reports
  • Honami Ogoh
  • ,
  • Kazutsune Yamagata
  • ,
  • Tomomi Nakao
  • ,
  • Lisa L Sandell
  • ,
  • Ayaka Yamamoto
  • ,
  • Aiko Yamashita
  • ,
  • Naomi Tanga
  • ,
  • Mai Suzuki
  • ,
  • Takaya Abe
  • ,
  • Issay Kitabayashi
  • ,
  • Toshio Watanabe
  • ,
  • Daisuke Sakai

7
1
開始ページ
11922
終了ページ
11922
記述言語
英語
掲載種別
DOI
10.1038/s41598-017-11745-5

Epigenetic regulation is required to ensure the precise spatial and temporal pattern of gene expression that is necessary for embryonic development. Although the roles of some epigenetic modifications in embryonic development have been investigated in depth, the role of methylation at lysine 79 (H3K79me) is poorly understood. Dot1L, a unique methyltransferase for H3K79, forms complexes with distinct sets of co-factors. To further understand the role of H3K79me in embryogenesis, we generated a mouse knockout of Mllt10, the gene encoding Af10, one Dot1L complex co-factor. We find homozygous Mllt10 knockout mutants (Mllt10-KO) exhibit midline facial cleft. The midfacial defects of Mllt10-KO embryos correspond to hyperterolism and are associated with reduced proliferation of mesenchyme in developing nasal processes and adjacent tissue. We demonstrate that H3K79me level is significantly decreased in nasal processes of Mllt10-KO embryos. Importantly, we find that expression of AP2α, a gene critical for midfacial development, is directly regulated by Af10-dependent H3K79me, and expression AP2α is reduced specifically in nasal processes of Mllt10-KO embryos. Suppression of H3K79me completely mimicked the Mllt10-KO phenotype. Together these data are the first to demonstrate that Af10-dependent H3K79me is essential for development of nasal processes and adjacent tissues, and consequent midfacial formation.

リンク情報
DOI
https://doi.org/10.1038/s41598-017-11745-5
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28931923
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607342