<scp>TET</scp>3–<scp>OGT</scp> interaction increases the stability and the presence of <scp>OGT</scp> in chromatin

Genes to Cells - Tập 19 Số 1 - Trang 52-65 - 2014
Ryo Ito1, Shogo Katsura2, Hiroki Shimada1, Hikaru Tsuchiya3, Masashi Hada2, Tomoko Asatsuma‐Okumura2, Akira Sugawara1, Atsushi Yokoyama1
1Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
2Research Center for Epigenetic Disease Institute of Molecular and Cellular Biosciences The University of Tokyo 1‐1‐1 Yayoi Bunkyo‐ku Tokyo 113‐0032 Japan
3Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan

Tóm tắt

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.

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Genes to Cells

Tập 19 Số 1

52-65

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