Human histone H3K79 methyltransferase DOT1L methyltransferase binds actively transcribing RNA polymerase II to regulate gene expression

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Title
Human histone H3K79 methyltransferase DOT1L methyltransferase binds actively transcribing RNA polymerase II to regulate gene expression
Author(s)
S K Kim; I Jung; H Lee; K Kang; Mirang Kim; K Jeong; C S Kwon; Y M Han; Yong Sung Kim; D Kim; D Lee
Bibliographic Citation
Journal of Biological Chemistry, vol. 287, no. 47, pp. 39698-39709
Publication Year
2012
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.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M112.384057
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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