Reference: Xiao T, et al. (2007) The RNA Polymerase II Kinase Ctk1 Regulates Positioning of a 5' Histone Methylation Boundary along Genes. Mol Cell Biol 27(2):721-31

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Abstract

In yeast and other eukaryotes, the histone methyltransferase Set1 mediates methylation of lysine 4 on histone H3 (H3K4me). This modification marks the 5' end of transcribed genes in a 5' to 3' tri- to di- to mono-methyl gradient, and promotes association of chromatin remodeling and histone modifying enzymes. Here we show that Ctk1, the serine 2 C-terminal domain (CTD) kinase for RNA polymerase II (RNAP II), regulates H3K4 methylation. We found that CTK1 deletion nearly abolished H3K4 monomethylation, yet caused a significant increase in H3K4 di- and trimethylation. Both on individual genes and genome-wide, the loss of CTK1 disrupted the H3K4 methylation patterns normally observed. H3K4me2 and H3K4me3 spread 3' into the body of genes, while H3K4 monomethylation was diminished. These effects were dependent on the catalytic activity of Ctk1, but are independent of Set2-mediated H3K36 methylation. Furthermore, these effects are not due to spurious transcription initiation in the body of genes, changes in RNAP II occupancy, changes in serine 5 CTD phosphorylation patterns, or to 'transcriptional stress'. These data show that Ctk1 acts to restrict the spread of H3K4 methylation through a mechanism that is independent of a general transcription defect. The evidence presented suggests that Ctk1 controls the maintenance of suppressive chromatin in the coding regions of genes by both promoting H3K36 methylation, which leads to histone deacetylation, and by preventing the 3' spread of H3K4 trimethylation, a mark associated with transcriptional initiation.

Reference Type
Journal Article
Authors
Xiao T, Shibata Y, Rao B, Laribee RN, O'Rourke R, Buck MJ, Greenblatt JF, Krogan NJ, Lieb JD, Strahl BD
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