Yang Chuhu, Bolotin Eugene, Jiang Tao, Sladek Frances M, Martinez Ernest
Genetics Genomics and Bioinformatics Graduate Program, University of California, Riverside, CA 92521, USA.
Gene. 2007 Mar 1;389(1):52-65. doi: 10.1016/j.gene.2006.09.029. Epub 2006 Oct 10.
The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that approximately 76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs - M3 (SCGGAAGY) and M22 (TGCGCANK) - that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only approximately 10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, approximately 46% of human core promoters contain the consensus INR (YYANWYY) and approximately 30% are INR-containing TATA-less genes. Significantly, approximately 46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present - and tend to cluster - in the transcription start site (TSS) region of approximately 40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic "housekeeping" processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription.
真核基因的核心启动子是招募基础转录机制以指导高效且准确转录起始的最小DNA区域。含有特定核心启动子元件（如TATA盒和起始子（INR））的人类和酵母基因的比例仍不清楚，且无TATA基因特有的核心启动子基序仍有待确定。在此，我们进行了全基因组规模的计算分析，结果表明约76%的人类核心启动子缺乏TATA样元件，GC含量高，且富含Sp1结合位点。我们进一步鉴定出两个基序——M3（SCGGAAGY）和M22（TGCGCANK）——它们优先出现在人类无TATA核心启动子中。约24%的人类基因具有TATA样元件，其启动子通常富含AT；然而，这些含TATA的启动子中只有约10%具有典型的TATA盒（TATAWAWR）。相比之下，约46%的人类核心启动子含有共有INR（YYANWYY），约30%是含INR的无TATA基因。值得注意的是，约46%的人类启动子既缺乏TATA样元件也缺乏共有INR元件。令人惊讶的是，哺乳动物类型的INR序列存在于约40%的酵母核心启动子的转录起始位点（TSS）区域，且倾向于聚集，特定核心启动子类型的频率在酵母和人类基因组中似乎是保守的。基因本体分析表明，与酵母一样，人类中的无TATA基因经常参与基本的“看家”过程，而含TATA的基因则更常受到高度调控，如受到生物或应激刺激的调控。这些结果揭示了酵母和人类中特定核心启动子类型的出现及其相关生物学过程存在意想不到的相似性，并指出了可能在不依赖TATA转录中起选择性作用的新型脊椎动物特异性DNA基序。
