The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development.
The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development.
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DOI：
10.1016/j.stem.2012.06.002
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发表时间：
2012-09-07
期刊：
影响因子：
23.9
通讯作者：
Hock, Hanno
中科院分区：
文献类型：
--
作者：
Qin, Jinzhong;Whyte, Warren A.;Anderssen, Endre;Apostolou, Effie;Chen, Hsu-Hsin;Akbarian, Schahram;Bronson, Roderick T.;Hochedlinger, Konrad;Ramaswamy, Sridhar;Young, Richard A.;Hock, Hanno
L3mbtl2与转录抑制和染色质压实有关，但其生物学功能尚未明确。本研究表明，L3mbtl2的破坏会导致胚胎死亡，并导致原肠胚形成失败。这与L3mbtl2−/−胚胎干（ES）细胞增殖受损和异常分化有关。L3mbtl2通过募集Polycomb suppressuppressicomplex1 （PRC1）相关复合体来调控基因，该复合体类似于前面描述的e2f6复合体，包括G9A、Hdac1和Ring1b。L3mbtl2在靶基因上的存在与h3k9二甲基化、低组蛋白乙酰化和h2ak119泛素化有关，但后者既不依赖于L3mbtl2，也不足以抑制。全基因组研究表明，l3mbtl2依赖性复合体主要调控不受典型PRC1和PRC2结合的基因。然而，一些发育调节因子被这三种复合物的联合活性所抑制。总之，我们发现非典型prc1家族复合体在胚胎干细胞和早期发育中具有高度选择性的重要作用。
L3mbtl2 has been implicated in transcriptional repression and chromatin compaction but its biological function has not been defined. Here we show that disruption of L3mbtl2 results in embryonic lethality with failure of gastrulation. This correlates with compromised proliferation and abnormal differentiation of L3mbtl2−/− embryonic stem (ES) cells. L3mbtl2 regulates genes by recruiting a Polycomb Repressive Complex1 (PRC1)-related complex, resembling the previously described E2F6-complex, and including G9A, Hdac1, and Ring1b. Presence of L3mbtl2 at target genes is associated with H3K9-dimethylation, low histone-acetylation, and H2AK119-ubiquitination, but the latter is neither dependent on L3mbtl2 nor sufficient for repression. Genome wide studies revealed that the L3mbtl2-dependent complex predominantly regulates genes not bound by canonical PRC1 and PRC2. However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development.
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DOI：
10.1042/bj20091439
发表时间：
2010-02-09
期刊：
The Biochemical journal
影响因子：
--
作者：
Lee J;Go Y;Kang I;Han YM;Kim J
通讯作者：
Kim J
影响因子：
10.5
作者：
Leeb, Martin;Pasini, Diego;Wutz, Anton
通讯作者：
Wutz, Anton
影响因子：
9.2
作者：
Pohlers, M;Truss, M;Hagemeier, C
通讯作者：
Hagemeier, C
影响因子：
64.5
作者：
Niwa, H;Toyooka, T;Rossant, J
通讯作者：
Rossant, J
影响因子：
64.5
作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
通讯作者：
Young RA