Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling
Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling
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DOI：
10.1016/j.ydbio.2010.02.023
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Poulin, Gino B.
中科院分区：
文献类型：
--
作者：
Fisher, Kate;Southall, Stacey M.;Poulin, Gino B.
保守的混合谱系白血病（MLL）复合体通过甲基转移酶（MT）活性在组蛋白尾部沉积活化的甲基标记。在这里，我们提供的活体证据表明，除了甲基化，秀丽隐杆线虫mll样复合体可以去除与转录抑制相关的特定甲基标记。这支持了MLL复合体协调甲基标记的沉积和去除以激活转录的提议模型。我们在大型RNAi筛选中发现了mll样复合体，旨在识别外阴发育过程中RAS信号的衰减者。我们还发现组蛋白乙酰转移酶复合物NuA4/TIP60与秀丽隐杆线虫mll样复合体合作抑制RAS信号。关键的是，我们发现这两个复合物调节RAS信号的一个共同的新靶点和衰减器，AJM-1 （Apical Junction Molecule-1）。因此，秀丽隐杆线虫mll样复合体与NuA4/TIP60复合体协同调节一种新的效应物AJM-1的表达。(C) 2010爱思唯尔公司版权所有。
The conserved Mixed Lineage Leukaemia (MLL) complex deposits activating methyl marks on histone tails through a methyltransferase (MT) activity. Here we provide in vivo evidence that in addition to methylation, the C. elegans MLL-like complex can remove specific methyl marks linked to repression of transcription. This supports the proposed model in which the MLL complex orchestrates both the deposition and the removal of methyl marks to activate transcription. We have uncovered the MLL-like complex in a large-scale RNAi screen designed to identify attenuators of RAS signalling during vulval development. We have also found that the histone acetyltransferase complex, NuA4/TIP60, cooperates with the C. elegans MLL-like complex in the attenuation of RAS signalling. Critically, we show that both complexes regulate a common novel target and attenuator of RAS signalling, AJM-1 (Apical Junction Molecule-1). Therefore, the C. elegans MLL-like complex cooperates with the NuA4/TIP60 complex to regulate the expression of a novel effector, AJM-1. (C) 2010 Elsevier Inc. All rights reserved.