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Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene

Genetics Genomics and Bioinformatics Graduate Program, University of California, Riverside, CA 92521, USA.
Gene (Impact Factor: 2.08). 04/2007; 389(1):52-65. DOI: 10.1016/j.gene.2006.09.029
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ABSTRACT 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.

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    • "The identification of DNA binding sites for transcription factors (motifs) is important for a complete understanding of co-regulation of gene expression, but still remains to be quite challenging to achieve. Two approaches dominate motif-finding algorithms: (1) the word-based way [1] [2] [3] that relies on exhaustive enumeration or counting frequencies and (2) the probabilistic way [4] [5] [6] that relies on optimizing a scalar-based scoring matrix [7] [8], which is visualized conveniently by a sequence "
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    Procedia Computer Science 12/2015; 51:602-609. DOI:10.1016/j.procs.2015.05.328
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    • "Moreover, analysis of promoter sequences (400 bp upstream of and 100 bp downstream from the TSS) of the up-regulated genes identified binding sites for factors regulated by p38 kinase activity such as JUN, JUND, ATF1, and CREB1 (Fig. 2C; Tan et al. 1996; Gao et al. 2013). In addition, we found an enrichment for the TATA box motif in promoter sequences of the upregulated genes (Fig. 2C), in agreement with the well-established role of this motif in the regulation of signal-inducible transcription (Basehoar et al. 2004; Yang et al. 2007). "
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    • "The TATA box is typically the main recognition sequence for RNA polII at the transcription start site [17]. In addition, most genes also contain initiator sequences that can fulfill the role of the promoter [18], [19]. The consensus initiator sequence is 5′-C/T-C/T-A+1-N-T/A-C/T-C/T-C/T, and it is not as highly conserved as the TATA box [20]. "
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