title: RE-IIBP Methylates H3K79 and Induces MEIS1-mediated Apoptosis via H2BK120 Ubiquitination by RNF20.
abstract: Histone lysine methylation contributes to transcriptional regulation by serving as a platform for the recruitment of various cofactors. Intense studies have been conducted for elucidating the functional meaning of H3K79 methylation, and to date, the only known HMTase responsible for the modification was DOT1L. In this study, we report that the MMSET isoform RE-IIBP has HMTase activity for H3K79. It was uncovered that RE-IIBP up-regulates MEIS1 transcription through H3K79 methylation via recruitment to the MEIS1 promoter. By means of proteomic and biochemical analysis, association of RE-IIBP with the E3 ubiquitin ligase RNF20 was demonstrated for synergistic activation of MEIS1 transcription via H3K79 HMTase activity. Furthermore, It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. These findings suggest RE-IIBP as another candidate for further studies to elucidate the mechanism of H3K79 methylation and its biological functions.
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Woo Park
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Kee-Beom
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Yun-Cheol
authors.initials: YC
authors.lastname: Chae
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Oh-Seok
authors.initials: OS
authors.lastname: Jeong
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases