Mannervik M, Levine M
Department of Molecular and Cellular Biology, Division of Genetics, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6797-801. doi: 10.1073/pnas.96.12.6797.
Previous studies have implicated histone deacetylation and chromatin condensation as critical mechanisms of transcription repression in yeast and mammals. A specific histone deacetylase, Rpd3, interacts with a variety of sequence-specific transcriptional repressors, including Mad-Max heterodimers and members of the nuclear receptor superfamily. Here, we present evidence that a strong hypomorphic mutation in the Drosophila Rpd3 gene causes embryonic lethality and a specific pair-rule segmentation phenotype. The analysis of a number of segmentation genes suggests that the repressor function of Even-skipped (Eve) may be diminished, causing an indirect loss of Ftz-mediated activation of engrailed. The relatively mild defects observed in Rpd3 mutants suggest that the recently identified Groucho and dCtBP corepressor proteins do not function solely through the recruitment of histone deacetylases. We discuss the possibility that Eve mediates multiple mechanisms of repression, so that Rpd3 mutants disrupt the regulation of just a subset of Eve target genes.
以往的研究表明，组蛋白去乙酰化和染色质浓缩是酵母和哺乳动物中转录抑制的关键机制。一种特定的组蛋白去乙酰化酶Rpd3，可与多种序列特异性转录抑制因子相互作用，包括Mad-Max异源二聚体和核受体超家族成员。在此，我们提供证据表明，果蝇Rpd3基因中的一个强亚效突变会导致胚胎致死和特定的成对规则节段表型。对多个节段基因的分析表明，Even-skipped（Eve）的抑制功能可能会减弱，从而导致Ftz介导的engrailed激活间接丧失。在Rpd3突变体中观察到的相对较轻的缺陷表明，最近鉴定出的Groucho和dCtBP共抑制蛋白并非仅通过募集组蛋白去乙酰化酶发挥作用。我们讨论了Eve介导多种抑制机制的可能性，因此Rpd3突变体仅破坏了Eve靶基因子集的调控。
