Boube M, Faucher C, Joulia L, Cribbs D L, Bourbon H M
Centre de Biologie du Développement-CNRS, 31062 Toulouse CEDEX 04, France.
Genes Dev. 2000 Nov 15;14(22):2906-17. doi: 10.1101/gad.17900.
The origins of specificity in gene expression are a central concern in understanding developmental control. Mediator protein complexes regulate transcriptional initiation, acting as modular adaptors linking specific transcription factors to core RNA polymerase II. Here, we identified the Drosophila homologs of 23 human mediator genes and mutations of two, dTRAP240 and of dTRAP80 (the putative fly homolog of yeast SRB4). Clonal analysis indicates a general role for dTRAP80 necessary for cell viability. The dTRAP240 gene is also essential, but cells lacking its function are viable and proliferate normally. Clones reveal localized developmental activities including a sex comb cell identity function. This contrasts with the ubiquitous nuclear accumulation of dTRAP240 protein in imaginal discs. Synergistic genetic interactions support shared developmental cell and segment identity functions of dTRAP240 and dTRAP80, potentially within a common complex. Further, they identify the homeotic Sex combs reduced product, required for the same cell/tissue identities, as a functional partner of these mediator proteins.
基因表达特异性的起源是理解发育控制的核心问题。中介蛋白复合物调节转录起始,作为将特定转录因子与核心RNA聚合酶II连接起来的模块化衔接子。在这里,我们鉴定了23个人类中介基因的果蝇同源物以及其中两个基因dTRAP240和dTRAP80(推测为酵母SRB4的果蝇同源物)的突变。克隆分析表明dTRAP80对细胞存活具有普遍作用。dTRAP240基因也是必需的,但缺乏其功能的细胞是存活的且能正常增殖。克隆显示出局部发育活性,包括性梳细胞身份功能。这与dTRAP240蛋白在成虫盘细胞核中普遍积累形成对比。协同遗传相互作用支持dTRAP240和dTRAP80在发育细胞和节段身份功能上的共享,可能在一个共同的复合物中。此外,他们鉴定了对相同细胞/组织身份必需的同源异型基因性梳减少产物,作为这些中介蛋白的功能伙伴。