Kunert Natascha, Wagner Eugenia, Murawska Magdalena, Klinker Henrike, Kremmer Elisabeth, Brehm Alexander
Institut für Molekularbiologie und Tumorforschung, Universität Marburg, Marburg, Germany.
EMBO J. 2009 Mar 4;28(5):533-44. doi: 10.1038/emboj.2009.3. Epub 2009 Jan 22.
The ATP-dependent chromatin remodeller Mi-2 functions as a transcriptional repressor and contributes to the suppression of cell fates during development in several model organisms. Mi-2 is the ATPase subunit of the conserved Nucleosome Remodeling and Deacetylation (NuRD) complex, and transcriptional repression by Mi-2 is thought to be dependent on its associated histone deacetylase. Here, we have purified a novel dMi-2 complex from Drosophila that is distinct from dNuRD. dMec (dMEP-1 complex) is composed of dMi-2 and dMEP-1. dMec is a nucleosome-stimulated ATPase that is expressed in embryos, larval tissues and adult flies. Surprisingly, dMec is far more abundant than dNuRD and constitutes the major dMi-2-containing complex. Both dNuRD and dMec associate with proneural genes of the achaete-scute complex. However, despite lacking a histone deacetylase subunit, only dMec contributes to the repression of proneural genes. These results reveal an unexpected complexity in the composition and function of Mi-2 complexes.
ATP 依赖的染色质重塑因子 Mi-2 作为转录抑制因子发挥作用，并在几种模式生物的发育过程中参与细胞命运的抑制。Mi-2 是保守的核小体重塑与去乙酰化（NuRD）复合体的 ATP 酶亚基，Mi-2 的转录抑制作用被认为依赖于其相关的组蛋白去乙酰化酶。在此，我们从果蝇中纯化出一种与 dNuRD 不同的新型 dMi-2 复合体。dMec（dMEP-1 复合体）由 dMi-2 和 dMEP-1 组成。dMec 是一种受核小体刺激的 ATP 酶，在胚胎、幼虫组织和成年果蝇中均有表达。令人惊讶的是，dMec 远比 dNuRD 丰富，并且构成了主要的含 dMi-2 复合体。dNuRD 和 dMec 都与无刚毛 - 毛撮复合体的神经原基因相关联。然而，尽管缺乏组蛋白去乙酰化酶亚基，但只有 dMec 参与神经原基因的抑制。这些结果揭示了 Mi-2 复合体在组成和功能上意想不到的复杂性。
