title: The ATF/CREB site is the key element for transcription of the human RNA methyltransferase like 1(RNMTL1) gene, a newly discovered 17p13.3 gene.
abstract: The human RNA methyltransferase like 1 gene (RNMTL1) is one of thirteen newly discovered genes within a 116 Kb segment of the chromosome 17p13.3 that suffers from a high frequent loss of heterozygosity in human hepatocellular carcinoma in China[1-5]. To understand the molecular mechanisms underlying transcription control of the RNMTL1 gene in human cancers, we decline using of the conventional approach where the cis-elements bound by the known transcription factors are primary targets, and carried out the systematic analyses to dissect the promoter structure and identify/characterize the key cis-elements that are responsible for its strong expression in cell. The molecular approaches applied included 1, the primer extension for mapping of the transcription starts; 2, the transient transfection/reporter assays on a large number of deletion and site-specific mutants of the promoter segment for defining the minimal promoter and the crucial elements within; and 3, the electrophoresis mobility shift assay with specific antibodies for reconfirming the nature of the transcription factors and their cognate cis-elements. We have shown that the interaction of an ATF/CREB element (-38 to -31) and its cognate transcription factors play a predominant role in the promoter activity of the RNMTL1 gene. The secondary DNA structures of the ATF/CREB element play a more vital role in the protein-DNA interaction. Finally, we reported a novel mechanism underlying the YY1 mediated transcription repression, namely, the ATF/CREB dependent transcription-repression by YY1 is executed in absence of its own sequence-specific binding.
authors.affiliation: The State-key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Xie-tu China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: De Zhu
authors.forename: Min
authors.initials: M
authors.lastname: Ni
authors.forename: Fang
authors.initials: F
authors.lastname: Wan
authors.forename: Jian Ren
authors.initials: JR
authors.lastname: Gu
mesh_terms: D051696:Activating Transcription Factors; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002886:Chromosomes, Human, Pair 17; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D051696:Activating Transcription Factors; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D012313:RNA; D008780:Methyltransferases