The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis.
The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis.
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DOI：
10.1186/1756-8935-2-5
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发表时间：
2009-04-06
影响因子：
3.9
通讯作者：
Stewart AF
中科院分区：
文献类型：
--
作者：
Glaser S;Lubitz S;Loveland KL;Ohbo K;Robb L;Schwenk F;Seibler J;Roellig D;Kranz A;Anastassiadis K;Stewart AF
组蛋白甲基化被认为是维持和限制多细胞生物体中细胞特性的表观遗传机制的核心。为了研究表观遗传学在细胞动态平衡中的作用，我们利用他莫昔芬诱导的Cre重组，在胚胎干细胞(ES)发育过程中和成年小鼠中有条件地突变了组蛋白3赖氨酸4甲基转移酶ML12。在ES细胞中，表达谱出人意料地显示只有一个基因Magoh2依赖于mll2，几乎没有其他基因受到影响。MLL2的缺失导致了Magoh2启动子上H3K4me3的缺失，并伴随着H3K27me3和DNA甲基化的获得。因此，与三胸果蝇同源的MLL2基因需要防止Magoh2启动子的多梳基团抑制，而抑制进一步伴随着DNA甲基化。在子宫中早期丢失的MLL2重现了在MLI2-/-胚胎中发现的胚胎致死性。然而，在E11.5之后，MLL2的缺失产生了没有显著病理变化的小鼠。因此，MLL2不是后期发育、干细胞或体细胞类型动态平衡所必需的。然而，它在生殖细胞谱系中是必需的。虽然精原细胞A仍然存在，但在移除MLL2后，精子发生丧失。这些数据提出了一个双峰招募和维持模型，在该模型中，MLL2需要在分化过程中建立某些表观遗传决定，然后通过多余的机制来维持这些决定。我们还认为这些机制与CpG岛启动子的表观遗传维持有关。
Histone methylation is thought to be central to the epigenetic mechanisms that maintain and confine cellular identity in multi-cellular organisms. To examine epigenetic roles in cellular homeostasis, we conditionally mutated the histone 3 lysine 4 methyltransferase, Mll2, in embryonic stem (ES) cells, during development and in adult mice using tamoxifen-induced Cre recombination. In ES cells, expression profiling unexpectedly revealed that only one gene, Magoh2, is dependent upon Mll2 and few other genes were affected. Loss of Mll2 caused loss of H3K4me3 at the Magoh2 promoter and concomitant gain of H3K27me3 and DNA methylation. Hence Mll2, which is orthologous to Drosophila Trithorax, is required to prevent Polycomb-Group repression of the Magoh2 promoter, and repression is further accompanied by DNA methylation. Early loss of Mll2 in utero recapitulated the embryonic lethality found in Mll2-/- embryos. However, loss of Mll2 after E11.5 produced mice without notable pathologies. Hence Mll2 is not required for late development, stem cells or homeostasis in somatic cell types. However it is required in the germ cell lineage. Spermatogenesis was lost upon removal of Mll2, although spermatogonia A persisted. These data suggest a bimodal recruit and maintain model whereby Mll2 is required to establish certain epigenetic decisions during differentiation, which are then maintained by redundant mechanisms. We also suggest that these mechanisms relate to the epigenetic maintenance of CpG island promoters.
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影响因子：
4.6
作者：
Hameyer, Dorothe;Loonstra, Ate;Bockamp, Ernesto
通讯作者：
Bockamp, Ernesto
影响因子：
64.5
作者：
HAY, B;JAN, LY;JAN, YN
通讯作者：
JAN, YN
影响因子：
14.9
作者：
Indra, AK;Warot, X;Metzger, D
通讯作者：
Metzger, D
DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
Feil, R;Wagner, J;Chambon, P
通讯作者：
Chambon, P
影响因子：
4.8
作者：
Lee, JH;Skalnik, DG
通讯作者：
Skalnik, DG