Pollock R, Treisman R
Transcription Laboratory, Imperial Cancer Research Fund Laboratories, London, UK.
Genes Dev. 1991 Dec;5(12A):2327-41. doi: 10.1101/gad.5.12a.2327.
Serum response factor (SRF) is a transcription factor that binds the sequence CC(A/T)6GG found in a number of growth factor-inducible and muscle-specific promoters. We describe the isolation and characterization of cDNA clones encoding a family of three human SRF-related DNA-binding proteins. Each of these RSRF (related to SRF) proteins contains an 86-amino-acid amino-terminal region related to the SRF DNA-binding domain: In RSRFC4 and RSRFC9, this region is identical, whereas that present in RSRFR2 differs by seven conservative amino acid substitutions. The DNA-binding specificity of the RSRF proteins, which recognize the consensus sequence CTA(A/T)4TAG, is distinct from that of SRF. The entire RSRF common region is required for DNA binding, and the differential sequence specificity of the RSRFs and SRF is the result of differences in the basic amino-terminal part of this domain. The RSRF proteins bind DNA as dimers and can dimerize with one another but not with SRF. Although the RSRF mRNAs are expressed in many cell types, RSRFR2 mRNA is expressed at elevated levels in several B-cell lines. Consistent with this, extracts from many cell types form CTA(A/T)4TAG-binding complexes that contain RSRF proteins, and oligonucleotides containing RSRF-binding sites function as promoter elements in transfection assays. Like SRF-binding sites, RSRF-binding sites are found in the regulatory sequences of a number of growth factor-inducible and muscle-specific genes, and we show that RSRF polypeptides are components of previously characterized binding activities that interact with these elements. We discuss the potential role of RSRF proteins in the regulation of these genes.
血清反应因子（SRF）是一种转录因子，它能结合许多生长因子诱导型和肌肉特异性启动子中发现的CC(A/T)6GG序列。我们描述了编码三种人类SRF相关DNA结合蛋白家族的cDNA克隆的分离和特性。这些RSRF（与SRF相关）蛋白中的每一种都包含一个与SRF DNA结合结构域相关的86个氨基酸的氨基末端区域：在RSRFC4和RSRFC9中，该区域是相同的，而RSRFR2中存在的区域有七个保守氨基酸取代。RSRF蛋白识别共有序列CTA(A/T)4TAG的DNA结合特异性与SRF不同。DNA结合需要整个RSRF共同区域，RSRF和SRF的不同序列特异性是该结构域基本氨基末端部分差异的结果。RSRF蛋白以二聚体形式结合DNA，并且可以彼此二聚化，但不能与SRF二聚化。尽管RSRF mRNA在许多细胞类型中表达，但RSRFR2 mRNA在几种B细胞系中表达水平升高。与此一致的是，许多细胞类型的提取物形成含有RSRF蛋白的CTA(A/T)4TAG结合复合物，并且含有RSRF结合位点的寡核苷酸在转染试验中起启动子元件的作用。与SRF结合位点一样，RSRF结合位点存在于许多生长因子诱导型和肌肉特异性基因的调控序列中，并且我们表明RSRF多肽是先前表征的与这些元件相互作用的结合活性的组成部分。我们讨论了RSRF蛋白在这些基因调控中的潜在作用。
