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经典 H2A 同种型丝氨酸 40 位上新 O-GlcNAc 糖基化修饰，特异性存在于有胎盘生物中。

Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity.

机构信息

Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.

Waseda Research Institute for Science and Engineering, Waseda University Tokyo 169-8555, JAPAN.

出版信息

Sci Rep. 2016 Sep 12;6:31785. doi: 10.1038/srep31785.

DOI:10.1038/srep31785
PMID:27615797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5018834/
Abstract

We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. Genome database surveys revealed that Ser(40) isoforms of H2A emerged in Marsupialia and persisted thereafter in mammals. We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals.

摘要

我们在此报告新发现的组蛋白 H2A 丝氨酸 40 位的 O-连接-N-乙酰葡萄糖胺（O-GlcNAc）修饰（H2AS40Gc）。小鼠基因组含有 18 种 H2A 异构体，其中 13 种具有丝氨酸 40 位，另外 5 种具有丙氨酸 40 位。单克隆抗体的生产以及与反相（RP）高效液相色谱（HPLC）分级相结合的质谱分析表明，O-GlcNAcylation 是特异性针对丝氨酸 40 位异构体的。H2AS40Gc 位点位于 L1 环结构中，两个 H2A 分子在核小体中相互作用。H2AS40Gc 的靶标分布在整个基因组中，并在小鼠滋养层干细胞的分化过程中发生显著变化。除了小鼠，H2AS40Gc 还在人类、猕猴和奶牛中被检测到，而只具有丙氨酸 40 位异构体的非哺乳动物，如蚕、斑马鱼和非洲爪蟾，则没有信号。基因组数据库调查显示，H2A 的丝氨酸 40 位异构体出现在有袋动物中，并在此后一直存在于哺乳动物中。我们提出，H2A 丝氨酸 40 位及其 O-GlcNAcylation 的出现将遗传事件与与胎盘动物进化相关的全基因组表观遗传事件联系起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/1e9fa494de5b/srep31785-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/19a19913607c/srep31785-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/6647dba68f64/srep31785-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/8edb630dde80/srep31785-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/86c556a8e275/srep31785-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/1e9fa494de5b/srep31785-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/19a19913607c/srep31785-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/6647dba68f64/srep31785-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/8edb630dde80/srep31785-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/86c556a8e275/srep31785-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0a/5018834/1e9fa494de5b/srep31785-f5.jpg

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