Overlapping ETS and CRE Motifs (G/CCGGAAGTGACGTCA) Preferentially Bound by GABPα and CREB Proteins

G3: Genes, Genomes, Genetics

Charles Vinson⁴  Ishminder Mann⁴  Raghunath Chatterjee⁴  Jianfei Zhao⁴  Andrey Shlyakhtenko⁴  B. K. Sathyanarayana¹  Joshua J. Waterfall³  Paul Meltzer³  Ximiao He⁴  Peter C. FitzGerald² 

[1] Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892;Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892;Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892;Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

关键词: proximal promoters;    transcription factor binding sites;    co-localization;    transcriptional start site;    EMSA;   

DOI  :  10.1534/g3.112.004002

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Previously, we identified 8-bps long DNA sequences (8-mers) that localize in human proximal promoters and grouped them into known transcription factor binding sites (TFBS). We now examine split 8-mers consisting of two 4-mers separated by 1-bp to 30-bps (X₄-N_1-30-X₄) to identify pairs of TFBS that localize in proximal promoters at a precise distance. These include two overlapping TFBS: the ETS⇔ETS motif (^C/_GCCGGAAGCGGAA) and the ETS⇔CRE motif (^C/_GCGGAAGTGACGTCAC). The nucleotides in bold are part of both TFBS. Molecular modeling shows that the ETS⇔CRE motif can be bound simultaneously by both the ETS and the B-ZIP domains without protein-protein clashes. The electrophoretic mobility shift assay (EMSA) shows that the ETS protein GABPα and the B-ZIP protein CREB preferentially bind to the ETS⇔CRE motif only when the two TFBS overlap precisely. In contrast, the ETS domain of ETV5 and CREB interfere with each other for binding the ETS⇔CRE. The 11-mer (CGGAAGTGACG), the conserved part of the ETS⇔CRE motif, occurs 226 times in the human genome and 83% are in known regulatory regions. In vivo GABPα and CREB ChIP-seq peaks identified the ETS⇔CRE as the most enriched motif occurring in promoters of genes involved in mRNA processing, cellular catabolic processes, and stress response, suggesting that a specific class of genes is regulated by this composite motif.

【 授权许可】

Unknown