RRC ID 35795
Author Ito R, Katsura S, Shimada H, Tsuchiya H, Hada M, Okumura T, Sugawara A, Yokoyama A.
Title TET3-OGT interaction increases the stability and the presence of OGT in chromatin.
Journal Genes Cells
Abstract Gene expression is controlled by alterations in the epigenome, including DNA methylation and histone modification. Recently, it was reported that 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by proteins in the ten-eleven translocation (TET) family. This conversion is believed to be part of the mechanism by which methylated DNA is demethylated. Moreover, histones undergo modifications such as phosphorylation and acetylation. In addition, modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase (OGT) was recently identified as a novel histone modification. Herein, we focused on TET3, the regulation of which is still unclear. We attempted to elucidate the mechanism of its regulation by biochemical approaches. First, we conducted mass spectrometric analysis in combination with affinity purification of FLAG-TET3, which identified OGT as an important partner of TET3. Co-immunoprecipitation assays using a series of deletion mutants showed that the C-terminal H domain of TET3 was required for its interaction with OGT. Furthermore, we showed that TET3 is GlcNAcylated by OGT, although the GlcNAcylation did not affect the global hydroxylation of methylcytosine by TET3. Moreover, we showed that TET3 enhanced its localization to chromatin through the stabilization of OGT protein. Taken together, we showed a novel function of TET3 that likely supports the function of OGT.
Volume 19(1)
Pages 52-65
Published 2014-1
DOI 10.1111/gtc.12107
PMID 24304661
MeSH Animals Cell Culture Techniques Chromatin / chemistry* Chromatin / metabolism DNA-Binding Proteins / chemistry* DNA-Binding Proteins / metabolism Dioxygenases / chemistry* Dioxygenases / metabolism Humans Mice N-Acetylglucosaminyltransferases / chemistry* N-Acetylglucosaminyltransferases / metabolism Protein Stability Proto-Oncogene Proteins / chemistry* Proto-Oncogene Proteins / metabolism
IF 2.048
Times Cited 28
WOS Category GENETICS & HEREDITY CELL BIOLOGY
Resource
DNA material CS-RfA-CG (RDB04390) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).