Tet Proteins Connect the O-Linked N-acetylglucosamine Transferase Ogt to Chromatin in Embryonic Stem Cells

被引：256
|
作者：
Vella, Pietro [1 ]
Scelfo, Andrea [1 ]
Jammula, SriGanesh [1 ]
Chiacchiera, Fulvio [1 ]
Williams, Kristine [2 ,3 ]
Cuomo, Alessandro [1 ]
Roberto, Alessandra [1 ]
Christensen, Jesper [2 ,3 ]
Bonaldi, Tiziana [1 ]
Helin, Kristian [2 ,3 ,4 ]
Pasini, Diego [1 ]
机构：
[1] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy
[2] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen, Denmark
[3] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen, Denmark
[4] Univ Copenhagen, Danish Stem Cell Ctr, DK-2200 Copenhagen, Denmark
来源：
MOLECULAR CELL | 2013年 / 49卷 / 04期
基金：
新加坡国家研究基金会;
关键词：
REPRESSIVE COMPLEX 2; GLCNAC TRANSFERASE; DNA METHYLATION; TRANSCRIPTION FACTORS; CYTOSOLIC PROTEINS; 5-HYDROXYMETHYLCYTOSINE; GLYCOSYLATION; NUCLEAR; GLCNACYLATION; WIDE;
D O I：
10.1016/j.molcel.2012.12.019
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
O-linked N-acetylglucosamine (O-GIcNAc) transferase (Ogt) activity is essential for embryonic stem cell (ESC) viability and mouse development. Ogt is present both in the cytoplasm and the nucleus of different cell types and catalyzes serine and threonine glycosylation. We have characterized the biochemical features of nuclear Ogt and identified the ten-eleven translocation (TET) proteins Tet1 and Tet2 as stable partners of Ogt in the nucleus of ESCs. We show at a genome-wide level that Ogt preferentially associates with Teti to genes promoters in close proximity of CpG-rich transcription start sites. These regions are characterized by low levels of DNA modification, suggesting a link between Teti and Ogt activities in regulating CpG island nnethylation. Finally, we show that Teti is required for binding of Ogt to chromatin affecting Teti activity. Taken together, our data characterize how O-GIcNAcylation is recruited to chromatin and interacts with the activity of 5-methylcytosine hydroxylases.
引用
收藏
页码：645 / 656
页数：12
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