Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2010 Apr 13;5(4):e10166. doi: 10.1371/journal.pone.0010166.
Groucho (Gro) is a Drosophila melanogaster transcriptional corepressor that directly interacts with the histone deacetylase Rpd3. Although previous studies suggest that this interaction is required for repression of Gro-responsive reporters in cultured cells, the in vivo significance of this interaction and the mechanism by which it leads to repression remain largely unexplored. In this study, we show that Gro is partially dependent on Rpd3 for repression, supporting the idea that Rpd3-mediated repression is one mode of Gro-mediated repression. We demonstrate that Gro colocalizes with Rpd3 to the chromatin of a target gene and that this is accompanied by the deacetylation of specific lysines within the N-terminal tails of histones H3 and H4. Gro overexpression leads to wing patterning defects and ectopic repression in the wing disc of transcription directed by the vestigial quadrant enhancer. These effects are reversed by the histone deacetylase inhibitors TSA and HC-Toxin and by the reduction of Rpd3 gene dosage. Furthermore, repression of the vestigial quadrant enhancer is accompanied by a Gro-mediated increase in nucleosome density, an effect that is reversed by histone deacetylase inhibitors. We propose a model in which Gro-mediated histone deacetylation results in increased nucleosome density leading to transcriptional repression.
格罗（Gro）是一种果蝇黑色素体转录核心抑制剂，它可以直接与组蛋白去乙酰化酶 Rpd3 相互作用。尽管之前的研究表明，这种相互作用对于培养细胞中 Gro 反应报告基因的抑制是必需的，但这种相互作用的体内意义及其导致抑制的机制在很大程度上仍未得到探索。在本研究中，我们表明 Gro 部分依赖于 Rpd3 进行抑制，支持了 Rpd3 介导的抑制是 Gro 介导的抑制的一种模式的观点。我们证明 Gro 与 Rpd3 共定位于靶基因的染色质上，并且伴随着组蛋白 H3 和 H4 的 N 端尾巴内的特定赖氨酸的去乙酰化。Gro 的过表达导致翅膀模式缺陷和 vestigial 四分之一增强子指导的翅膀盘中的异位抑制。这些效应可被组蛋白去乙酰化酶抑制剂 TSA 和 HC-Toxin 以及 Rpd3 基因剂量的降低所逆转。此外，vestigial 四分之一增强子的抑制伴随着 Gro 介导的核小体密度增加，该效应可被组蛋白去乙酰化酶抑制剂逆转。我们提出了一个模型，其中 Gro 介导的组蛋白去乙酰化导致核小体密度增加，从而导致转录抑制。
