Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

Tomizawa Shin-ichi; Kobayashi Yuki; Shirakawa Takayuki; Watanabe Kumiko; Mizoguchi Keita; Hoshi Ikue; Nakajima Kuniko; Nakabayashi Jun; Singh Sukhdeep; Dahl Andreas; Alexopoulou Dimitra; Seki Masahide; Suzuki Yutaka; Royo Helene; Peters Antoine H. F. M.; Anastassiadis Konstantinos; Stewart A. Francis; Ohbo Kazuyuki

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Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

机译：KMT2B在种系和胚胎启动子的小鼠精牙科干细胞中传送单价和二价H3K4ME3

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The mammalian male germline is sustained by a pool of spermatogonial stem cells (SSCs) that can transmit both genetic and epigenetic information to offspring. However, the mechanisms underlying epigenetic transmission remain unclear. The histone methyltransferase Kmt2b is highly expressed in SSCs and is required for the SSC-to-progenitor transition. At the stem-cell stage, Kmt2b catalyzes H3K4me3 at bivalent H3K27me3-marked promoters as well as at promoters of a new class of genes lacking H3K27me3, which we call monovalent. Monovalent genes are mainly activated in late spermatogenesis, whereas most bivalent genes are mainly not expressed until embryonic development. These data suggest that SSCs are epigenetically primed by Kmt2b in two distinguishable ways for the upregulation of gene expression both during the spermatogenic program and through the male germline into the embryo. Because Kmt2b is also the major H3K4 methyltransferase for bivalent promoters in embryonic stem cells, we also propose that Kmt2b has the capacity to prime stem cells epigenetically.

机译：哺乳动物雄性种系由一群精术干细胞（SSCs）维持，可以将遗传和表观遗传信息传送到后代。然而，表观遗传传播的机制仍然不清楚。组蛋白甲基转移酶KMT2B在SSCs中高度表达，并且对于SSC-祖的转变需要。在茎细胞阶段，KMT2B催化在二价H3K27ME3标记的启动子上，以及缺乏H3K27ME3的新类基因的启动子，我们称之为单价。单价基因主要在晚期精子发生中被激活，而大多数二价基因主要没有表达直至胚胎发育。这些数据表明SSCS在PRMT2B中以两种可区分方式进行了近似的，用于在精子发生过程中并通过雄性种系为胚胎中的基因表达。由于KMT2B也是胚胎干细胞的二价促进剂的主要H3K4甲基转移酶，因此我们还提出了KMT2B的能力在表现出延伸的干细胞。

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来源
《Development》 |2018年第23期|共10页
作者
Tomizawa Shin-ichi; Kobayashi Yuki; Shirakawa Takayuki; Watanabe Kumiko; Mizoguchi Keita; Hoshi Ikue; Nakajima Kuniko; Nakabayashi Jun; Singh Sukhdeep; Dahl Andreas; Alexopoulou Dimitra; Seki Masahide; Suzuki Yutaka; Royo Helene; Peters Antoine H. F. M.; Anastassiadis Konstantinos; Stewart A. Francis; Ohbo Kazuyuki;
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作者单位

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

Yokohama City Univ Adv Med Res Ctr Bioinformat Lab Sch Med Yokohama Kanagawa 2360004 Japan;

Tech Univ Dresden Biotechnol Ctr Ctr Mol &

Cellular Bioengn Tatzberg 47-51 D-01307 Dresden;

Tech Univ Dresden Genome Ctr Ctr Mol &

Cellular Bioengn Tatzberg 47-51 D-01307 Dresden Germany;

Tech Univ Dresden Genome Ctr Ctr Mol &

Cellular Bioengn Tatzberg 47-51 D-01307 Dresden Germany;

Univ Tokyo Grad Sch Frontier Sci Dept Computat Biol &

Med Sci Chiba 2778562 Japan;

Univ Tokyo Grad Sch Frontier Sci Dept Computat Biol &

Med Sci Chiba 2778562 Japan;

Friedrich Miescher Inst Biomed Res CH-4058 Basel Switzerland;

Friedrich Miescher Inst Biomed Res CH-4058 Basel Switzerland;

Tech Univ Dresden Biotechnol Ctr Ctr Mol &

Cellular Bioengn Tatzberg 47-51 D-01307 Dresden;

Tech Univ Dresden Biotechnol Ctr Ctr Mol &

Cellular Bioengn Tatzberg 47-51 D-01307 Dresden;

Yokohama City Univ Sch Med Dept Histol &

Cell Biol Yokohama Kanagawa 2360004 Japan;

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正文语种 eng
中图分类人体形态学;
关键词
Spermatogenesis; Spermatogonia; Stem cells; Priming; Histone; Chromatin; Mouse;

机译：精子发生;精子;干细胞;灌注;组蛋白;染色质;小鼠;

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专利

1. Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters [J] . Tomizawa Shin-ichi, Kobayashi Yuki, Shirakawa Takayuki, Development . 2018,第23期

机译：KMT2B在种系和胚胎启动子的小鼠精牙科干细胞中传送单价和二价H3K4ME3
2. Bivalent promoter hypermethylation in cancer is linked to the H327me3/H3K4me3 ratio in embryonic stem cells [J] . Donnchadh S. Dunican, Heidi K. Mjoseng, Leanne Duthie, BMC Biology . 2020,第1期

机译：癌症中的二价促进剂高甲基化与胚胎干细胞中的H327ME3 / H3K4ME3比率有关
3. The Mll2 branch of the COMPASS family regulates bivalent promoters in mouse embryonic stem cells [J] . Hu D., Garruss A.S., Gao X., Nature structural & molecular biology . 2013,第9期

机译：COMPASS家族的Mll2分支调节小鼠胚胎干细胞中的二价启动子
4. Comparative Analysis of Bivalent Domains in Mammalian Embryonic Stem Cells [C] . Anna Mantsoki, Anagha Joshi International Conference on Bioinformatics and Biomedical Engineering . 2015

机译：哺乳动物胚胎干细胞中二价域的比较分析
5. Involvement of Wnt signalling pathways in the cell fate regulation of mouse spermatogonial stem cells [D] . Yeh, Jonathan R. 2012

机译：Wnt信号通路参与小鼠精原干细胞的细胞命运调控
6. Bivalent promoter hypermethylation in cancer is linked to the H327me3/H3K4me3 ratio in embryonic stem cells [O] . Donnchadh S. Dunican, Heidi K. Mjoseng, Leanne Duthie, 2020

机译：癌症中的二价启动子高甲基化与胚胎干细胞中的H327me3 / H3K4me3比相关
7. CpG island erosion, polycomb occupancy and sequence motif enrichment at bivalent promoters in mammalian embryonic stem cells [O] . Mantsoki, Anna, Devailly, Guillaume, Joshi, Anagha 2015

机译：CpG岛侵蚀，多梳占据和哺乳动物胚胎干细胞中二价启动子的序列基序富集

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

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