De Rubertis F, Kadosh D, Henchoz S, Pauli D, Reuter G, Struhl K, Spierer P
Department of Zoology and Animal Biology, University of Geneva, Switzerland.
Nature. 1996 Dec 12;384(6609):589-91. doi: 10.1038/384589a0.
Both position-effect variegation (PEV) in Drosophila and telomeric position-effect in yeast (TPE) result from the mosaic inactivation of genes relocated next to a block of centromeric heterochromatin or next to telomeres. In many aspects, these phenomena are analogous to other epigenetic silencing mechanisms, such as the control of homeotic gene clusters, X-chromosome inactivation and imprinting in mammals, and mating-type control in yeast. Dominant mutations that suppress or enhance PEV are thought to encode either chromatin proteins or factors that directly affect chromatin structure. We have identified an insertional mutation in Drosophila that enhances PEV and reduces transcription of the gene in the eye-antenna imaginal disc. The gene corresponds to that encoding the transcriptional regulator RPD3 in yeast, and to a human histone deacetylase. In yeast, RRD3-deletion strains show enhanced TPE, suggesting a conserved role of the histone deacetylase RPD3 in counteracting genomic silencing. This function of RPD3, which is in contrast to the general correlation between histone acetylation and increased transcription, might be due to a specialized chromatin structure at silenced loci.
果蝇中的位置效应斑驳（PEV）和酵母中的端粒位置效应（TPE）都是由于基因镶嵌失活导致的，这些基因被重新定位到靠近着丝粒异染色质区域或端粒附近。在许多方面，这些现象类似于其他表观遗传沉默机制，如哺乳动物中同源异型基因簇的调控、X染色体失活和印记，以及酵母中的交配型控制。抑制或增强PEV的显性突变被认为编码染色质蛋白或直接影响染色质结构的因子。我们在果蝇中鉴定出一个插入突变，它增强了PEV并降低了眼-触角成虫盘基因的转录。该基因与酵母中编码转录调节因子RPD3的基因相对应，也与人类组蛋白脱乙酰基酶相对应。在酵母中，RRD3缺失菌株显示出增强的TPE，这表明组蛋白脱乙酰基酶RPD3在对抗基因组沉默方面具有保守作用。RPD3的这种功能与组蛋白乙酰化和转录增加之间的一般相关性相反，可能是由于沉默位点处的特殊染色质结构所致。
