Tokusumi Yumiko, Ma Ying, Song Xianzhou, Jacobson Raymond H, Takada Shinako
Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Unit 1000, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Mol Cell Biol. 2007 Mar;27(5):1844-58. doi: 10.1128/MCB.01363-06. Epub 2007 Jan 8.
The core promoter is a critical DNA element required for accurate transcription and regulation of transcription. Several core promoter elements have been previously identified in eukaryotes, but those cannot account for transcription from most RNA polymerase II-transcribed genes. Additional, as-yet-unidentified core promoter elements must be present in eukaryotic genomes. From extensive analyses of the hepatitis B virus X gene promoter, here we identify a new core promoter element, XCPE1 (the X gene core promoter element 1), that drives RNA polymerase II transcription. XCPE1 is located between nucleotides -8 and +2 relative to the transcriptional start site (+1) and has a consensus sequence of G/A/T-G/C-G-T/C-G-G-G/A-A-G/C(+1)-A/C. XCPE1 shows fairly weak transcriptional activity alone but exerts significant, specific promoter activity when accompanied by activator-binding sites. XCPE1 is also found in the core promoter regions of about 1% of human genes, particularly in poorly characterized TATA-less genes. Our in vitro transcription studies suggest that the XCPE1-driven transcription can be highly active in the absence of TFIID because it can utilize either free TBP or the complete TFIID complex. Our findings suggest the possibility of the existence of a TAF1 (TFIID)-independent transcriptional initiation mechanism that may be used by a category of TATA-less promoters in higher eukaryotes.
核心启动子是精确转录和转录调控所必需的关键DNA元件。此前在真核生物中已鉴定出几种核心启动子元件,但这些元件无法解释大多数RNA聚合酶II转录基因的转录情况。真核生物基因组中必定存在其他尚未鉴定的核心启动子元件。通过对乙型肝炎病毒X基因启动子的广泛分析,我们在此鉴定出一种新的核心启动子元件XCPE1(X基因核心启动子元件1),它可驱动RNA聚合酶II转录。XCPE1相对于转录起始位点(+1)位于核苷酸-8至+2之间,共有序列为G/A/T-G/C-G-T/C-G-G-G/A-A-G/C(+1)-A/C。单独的XCPE1显示出相当弱的转录活性,但当与激活剂结合位点一起时,会发挥显著的、特异性的启动子活性。在约1%的人类基因的核心启动子区域中也发现了XCPE1,尤其是在特征不明确的无TATA盒基因中。我们的体外转录研究表明,XCPE1驱动的转录在没有TFIID的情况下可以高度活跃,因为它可以利用游离的TBP或完整的TFIID复合物。我们的发现表明,可能存在一种不依赖TAF1(TFIID)的转录起始机制,高等真核生物中的一类无TATA盒启动子可能会使用这种机制。