Drosophila ESC-like can substitute for ESC and becomes required for Polycomb silencing if ESC is absent
Drosophila ESC-like can substitute for ESC and becomes required for Polycomb silencing if ESC is absent
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DOI：
10.1016/j.ydbio.2007.10.025
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Harte, Peter J.
中科院分区：
文献类型：
--
作者：
Kurzhals, Rebeccah L.;Tie, Feng;Harte, Peter J.
果蝇ESC样基因（escl）编码一种与ESC非常相似的蛋白质。与ESC一样，ESCL通过其WD区直接与E（Z）组蛋白甲基转移酶结合。与ESC相反，ESC在胚胎发生期间以最高水平存在，此后以低水平存在，ESCL在整个发育过程中和成人中持续存在。ESC/E（Z）复合物主要在胚胎发生期间以高水平存在，但ESCL/E（Z）复合物在整个发育过程中被发现。虽然在S2和Kc细胞中通过RNAi去除ESCL或ESC对E（Z）介导的组蛋白H3赖氨酸27（1- 13 K27）的甲基化几乎没有影响，但同时去除ESCL和ESC导致二-和三甲基-H3 K27的损失，表明ESC或ESCL对于体内H3 K27的二-和三甲基化是必要的和足够的。虽然S2细胞中的E（Z）复合物主要含有ESC，但在ESC缺失的S2细胞中，ESCL水平显著升高，并且ESCL取代E（Z）复合物中的ESC。escl中产生很少蛋白质的突变是可行的，没有表现出表型，但强烈增强了esc突变体的表型，表明它们具有相似的功能。esc escl双纯合子在幼虫期结束时死亡，表明众所周知的esc纯合子的“母体拯救”需要ESCL。此外，母体和合子的过度表达的escl完全挽救了esc无效突变胚胎，不含ESC蛋白的致死性，表明ESCL可以完全取代ESC在体内。因此，这些数据表明ESC和ESCL在体内E（Z）复合物中发挥相似的功能，如果不是相同的话。尽管如此，当esc正常表达时，escl似乎完全不表达，至少在发育成形态正常的可育成虫时是这样。此外，esc escl双突变体的幼虫致死率，以及escl突变体中缺乏表型，进一步表明在野生型（esc（+））动物中，对正常成体发育重要的是esc的胚后表达，而不是escl。因此，escl在发育过程中似乎起着后备作用，只有当正常esc表达受损时才变得重要。(c)2007年爱思唯尔公司All rights reserved.
The Drosophila esc-like gene (escl) encodes a protein very similar to ESC. Like ESC, ESCL binds directly to the E(Z) histone methyltransferase via its WD region. In contrast to ESC, which is present at highest levels during embryogenesis and low levels thereafter, ESCL is continuously present throughout development and in adults. ESC/E(Z) complexes are present at high levels mainly during embryogenesis but ESCL/E(Z) complexes are found throughout development. While depletion of either ESCL or ESC by RNAi in S2 and Kc cells has little effect on E(Z)-mediated methylation of histone H3 lysine 27 (1-13K27), simultaneous depletion of ESCL and ESC results in loss of di- and trimethyl-H3K27, indicating that either ESC or ESCL is necessary and sufficient for di- and trimethylation of H3K27 in vivo. While E(Z) complexes in S2 cells contain predominantly ESC, in ESC-depleted S2 cells, ESCL levels rise dramatically and ESCL replaces ESC in E(Z) complexes. A mutation in escl that produces very little protein is viable and exhibits no phenotypes but strongly enhances esc mutant phenotypes, suggesting they have similar functions. esc escl double homozygotes die at the end of the larval period, indicating that the well-known "maternal rescue" of esc homozygotes requires ESCL. Furthermore, maternal and zygotic over-expression of escl fully rescues the lethality of esc null mutant embryos that contain no ESC protein, indicating that ESCL can substitute fully for ESC in vivo. These data thus indicate that ESC and ESCL play similar if not identical functions in E(Z) complexes in vivo. Despite this, when esc is expressed normally, escl appears to be entirely dispensable, at least for development into morphologically normal fertile adults. Furthermore, the larval lethality of esc escl double mutants, together with the lack of phenotypes in the escl mutant, further suggests that in wild-type (esc(+)) animals it is the post-embryonic expression of esc, not escl, that is important for development of normal adults. Thus escl appears to function in a back-up capacity during development that becomes important only when normal esc expression is compromised. (c) 2007 Elsevier Inc. All rights reserved.