Baumann Douglas G, Gilmour David S
The Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Nucleic Acids Res. 2017 Oct 13;45(18):10481-10491. doi: 10.1093/nar/gkx676.
Ribosomal protein (RP) genes must be coordinately expressed for proper assembly of the ribosome yet the mechanisms that control expression of RP genes in metazoans are poorly understood. Recently, TATA-binding protein-related factor 2 (TRF2) rather than the TATA-binding protein (TBP) was found to function in transcription of RP genes in Drosophila. Unlike TBP, TRF2 lacks sequence-specific DNA binding activity, so the mechanism by which TRF2 is recruited to promoters is unclear. We show that the transcription factor M1BP, which associates with the core promoter region, activates transcription of RP genes. Moreover, M1BP directly interacts with TRF2 to recruit it to the RP gene promoter. High resolution ChIP-exo was used to analyze in vivo the association of M1BP, TRF2 and TFIID subunit, TAF1. Despite recent work suggesting that TFIID does not associate with RP genes in Drosophila, we find that TAF1 is present at RP gene promoters and that its interaction might also be directed by M1BP. Although M1BP associates with thousands of genes, its colocalization with TRF2 is largely restricted to RP genes, suggesting that this combination is key to coordinately regulating transcription of the majority of RP genes in Drosophila.
核糖体蛋白(RP)基因必须协调表达才能使核糖体正确组装,但后生动物中控制RP基因表达的机制仍知之甚少。最近,人们发现与TATA结合蛋白相关的因子2(TRF2)而非TATA结合蛋白(TBP)在果蝇RP基因的转录中发挥作用。与TBP不同,TRF2缺乏序列特异性DNA结合活性,因此TRF2被招募到启动子的机制尚不清楚。我们发现,与核心启动子区域相关的转录因子M1BP可激活RP基因的转录。此外,M1BP直接与TRF2相互作用,将其招募到RP基因启动子。利用高分辨率ChIP-exo分析了M1BP、TRF2和TFIID亚基TAF1在体内的结合情况。尽管最近的研究表明TFIID在果蝇中不与RP基因结合,但我们发现TAF1存在于RP基因启动子上,其相互作用可能也由M1BP介导。虽然M1BP与数千个基因相关,但它与TRF2的共定位在很大程度上仅限于RP基因,这表明这种组合是协调调控果蝇大多数RP基因转录的关键。