果蝇组蛋白去乙酰化酶HDAC1和HDAC3选择性调控形态发生素靶基因转录

Drosophila Histone Deacetylases 1 and 3 Selectively Regulate the Transcription of Morphogens Target Genes

在真核细胞中,组蛋白的乙酰化状态对于基因转录的正常进行具有重要的调控作用。组蛋白的乙酰化修饰由组蛋白乙酰转移酶(histone acetyltransferases,HATs)执行,这种修饰是动态的、可逆的,负责去乙酰化修饰的酶是组蛋白去乙酰化酶(histone deacetylases,HDACs),推测HDACs可能通过影响组蛋白的乙酰化状态在基因的转录过程中发挥调控作用。该文以组蛋白去乙酰化酶HDAC1和HDAC3为对象,研究了它们在果蝇翅膀发育过程中对Wg(Wingless)、Hh(Hedgehog)以及Dpp(Decapentaplegic)信号通路下游靶基因转录的调控作用。结果发现,HDAC1功能缺失可导致Dpp下游靶基因Omb(optomotor-blind)和Hh下游靶基因Ptc(patched)的表达上调。Real-time quantitative PCR(RT-q PCR)结果显示,在HDAC1基因敲除的果蝇中,Ptc、Ci(cubitus interruptus)以及Omb的转录水平增加。HDAC3缺失导致Sal(spalt)的表达上调。RT-q PCR结果证实了HDAC3基因敲除果蝇的Sal转录增加,同时发现Vg(vestigial)的转录下降。而过表达HDAC1或HDAC3对下游靶基因的表达则没有影响。综上所述,该研究表明,HDAC1和HDAC3可以选择性地调控形态发生素下游靶基因的转录。

In eukaryotic cells, histone acetylation plays an important role in the process of RNA transcription. The histone acetylation status is mainly regulated by two classes of enzymes： histone acetyltransferases（HATs） and histone deacetylases（HDACs）. Histone acetylation is carried out by HATs, and this modification is dynamic and can be reversed by HDACs. Thus, we can easily infer that HDACs may render some impact on gene transcription by controlling histone deacetylation. In the current study, we explored the potentialrole of HDAC1 and HDAC3 in the transcription of several target genes of Wg, Hh and Dpp during Drosophila wing development. Our results showed that Dpp target gene Omb（optomotor-blind） and Hh target gene Ptc（patched） were dramaticly increased upon loss of HDAC1. Real-time quantitative PCR（RT-q PCR） results showed up-regulation of Ptc, Ci（cubitus interruptus） and Omb transcription in HDAC1 mutant fly. As to HDAC3, our data indicated that HDAC3 knock-out resulted in increased expression of Dpp target gene Sal（spalt）. RT-q PCR results showed up-regulation of Sal and down-regulation of Vg transcription in HDAC3 mutant fly. However, either overexpression of HDAC1 or HDAC3 had no effect on the target genes expression of Wg, Hh and Dpp. Altogether, our results indicated that HDAC1 and HDAC3 selectively regulated the transcription of morphogens target genes.