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

Department of Biochemistry, University of California, Riverside, Riverside, California, United States
Gene (Impact Factor: 2.14). 04/2007; 389(1):52-65. DOI: 10.1016/j.gene.2006.09.029
Source: PubMed


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.

Download full-text


Available from: Ernest Martinez
  • Source
    • "Based on our sequence analysis, the ek1 gene promoter is a TATA-less, GC-rich promoter which probably belongs to the housekeeping gene family. This assumption is supported by the fact that approximately 76% of human TATA-less core promoters contain multiple Sp1 binding elements in the GC richsequences[30]and the ubiquitous Sp1 serves as a constitutive activator of housekeeping genes by recruiting TATA-binding protein (TBP) to the promoters without recognizable consensus TATA box[31,32]. The activity of putative ek1 promoter (-1966/+1) was initially assessed in HepG2, HCT116 and MCF-7 cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Ethanolamine kinase (EK) catalyzes the phosphorylation of ethanolamine, the first step in the CDP-ethanolamine pathway for the biosynthesis of phosphatidylethanolamine (PE). Human EK exists as EK1, EK2α and EK2β isoforms, encoded by two separate genes, named ek1 and ek2. EK activity is stimulated by carcinogens and oncogenes, suggesting the involvement of EK in carcinogenesis. Currently, little is known about EK transcriptional regulation by endogenous or exogenous signals, and the ek gene promoter has never been studied. Methodology/principal findings: In this report, we mapped the important regulatory regions in the human ek1 promoter. 5' deletion analysis and site-directed mutagenesis identified a Sp site at position (-40/-31) that was essential for the basal transcription of this gene. Treatment of HCT116 cells with trichostatin A (TSA), a histone deacetylase inhibitor, significantly upregulated the ek1 promoter activity through the Sp(-40/-31) site and increased the endogenous expression of ek1. Chromatin immunoprecipitation assay revealed that TSA increased the binding of Sp1, Sp3 and RNA polymerase II to the ek1 promoter in HCT116 cells. The effect of TSA on ek1 promoter activity was cell-line specific as TSA treatment did not affect ek1 promoter activity in HepG2 cells. Conclusion/significance: In conclusion, we showed that Sp1 and Sp3 are not only essential for the basal transcription of the ek1 gene, their accessibility to the target site on the ek1 promoter is regulated by histone protein modification in a cell line dependent manner.
    Full-text · Article · Jan 2016 · PLoS ONE
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The conventional way of identifying possible motif sequences in a DNA strand is to use representative scalar weight matrix for searching good match substring alignments. However, this approach, solely based on match alignment information, is susceptible to a high number of ambiguous sites or false positives if the motif sequences are not well conserved. A significant amount of time is then required to verify these sites for the suggested motifs. Hence in this paper, the use of mismatch alignment information in addition to match alignment information for DNA motif searching is proposed. The objective is to reduce the number of ambiguous false positives encountered in the DNA motif searching, thereby making the process more efficient for biologists to use.
    Full-text · Article · Dec 2015 · Procedia Computer Science
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Selectivity of transcriptional responses to extracellular cues is reflected by the deposition of stimulus-specific chromatin marks. Although histone H3 phosphorylation is a target of numerous signaling pathways, its role in transcriptional regulation still remains poorly understood. Here we report for the first time a genome-wide analysis of H3S28ph in the mammalian system in the context of stress signaling. We found that this mark targets as many as 50% of all stress induced genes, underlining its importance in signal-induced transcription. By combining ChIP-seq, RNA-seq and spectrometry we identified the factors involved in biological interpretation of this histone modification. We found that MSK1/2 mediated phosphorylation of H3S28 at stress-responsive promoters contributes to the dissociation of HDAC co-repressor complexes and thereby to enhanced local histone acetylation and subsequent transcriptional activation of stress-induced genes. Our data reveals a novel function of the H3S28ph mark in the activation of mammalian genes in response to MAP kinase pathway activation.
    Full-text · Article · Aug 2014 · Genome Research
Show more