title: Human histone H3K79 methyltransferase DOT1L protein [corrected] binds actively transcribing RNA polymerase II to regulate gene expression.
abstract: Histone-modifying enzymes play a pivotal role in gene expression and repression. In human, DOT1L (Dot1-like) is the only known histone H3 lysine 79 methyltransferase. hDOT1L is associated with transcriptional activation, but the general mechanism connecting hDOT1L to active transcription remains largely unknown. Here, we report that hDOT1L interacts with the phosphorylated C-terminal domain of actively transcribing RNA polymerase II (RNAPII) through a region conserved uniquely in multicellular DOT1 proteins. Genome-wide profiling analyses indicate that the occupancy of hDOT1L largely overlaps with that of RNAPII at actively transcribed genes, especially surrounding transcriptional start sites, in embryonic carcinoma NCCIT cells. We also find that C-terminal domain binding or H3K79 methylations by hDOT1L is important for the expression of target genes such as NANOG and OCT4 and a marker for pluripotency in NCCIT cells. Our results indicate that a functional interaction between hDOT1L and RNAPII targets hDOT1L and subsequent H3K79 methylations to actively transcribed genes.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Seung-Kyoon
authors.initials: SK
authors.lastname: Kim
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.forename: Hosuk
authors.initials: H
authors.lastname: Lee
authors.forename: Keunsoo
authors.initials: K
authors.lastname: Kang
authors.forename: Mirang
authors.initials: M
authors.lastname: Kim
authors.forename: Kwiwan
authors.initials: K
authors.lastname: Jeong
authors.forename: Chang Seob
authors.initials: CS
authors.lastname: Kwon
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
authors.forename: Daeyoup
authors.initials: D
authors.lastname: Lee
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D055106:Genome-Wide Association Study; D057809:HEK293 Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D006657:Histones; C473477:DOT1L protein, human; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II