title: Transcriptional activation of Mina by Sp1/3 factors.
abstract: Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors: Shangli
authors: S
authors: Lian
authors: Hari Hara S K
authors: HH
authors: Potula
authors: Meenu R
authors: MR
authors: Pillai
authors: Melanie
authors: M
authors: Van Stry
authors: Madoka
authors: M
authors: Koyanagi
authors: Linda
authors: L
authors: Chung
authors: Makiko
authors: M
authors: Watanabe
authors: Mark
authors: M
authors: Bix
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: C512207:Mina53 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D051705:Sp3 Transcription Factor; D008156:Luciferases