title: Zfp423 binds autoregulatory sites in p19 cell culture model.
abstract: Zfp423 is a 30 zinc finger transcription factor that forms regulatory complexes with EBF family members and factors targeted by canonical signaling pathways. Zfp423 mutations produce a range of developmental abnormalities in mice and humans related to the ciliopathies. Surprisingly, computational analysis of clustered Zfp423 and partner motifs in conserved genomic sequences predicts enrichment in Zfp423 and Ebf genes. In cell culture models selected for Zfp423 and EBF expression, we identify strong and reproducible occupancy of two Zfp423 intronic sites using chromatin immunoprecipitation with multiple independent antibodies. Both sites are significantly enriched in either quantitative PCR or massively parallel sequencing assays. A site in intron 5 acts as a classical enhancer in transient assays, but does not require the consensus motif for activity, suggesting a redundant or modulatory role for Zfp423 binding in this context. We speculate that Zfp423 may repress this enhancer as part of a developmental ratchet.
authors.affiliation: Departments of Medicine and Cellular and Molecular Medicine, Institute for Genomic Medicine and Moores UCSD Cancer Center, University of California San Diego School of Medicine, La Jolla, California, United States of America.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Cho
authors.forename: Chen-Jei
authors.initials: CJ
authors.lastname: Hong
authors.forename: Aiju
authors.initials: A
authors.lastname: Hou
authors.forename: Peter M
authors.initials: PM
authors.lastname: Gent
authors.forename: Kuixing
authors.initials: K
authors.lastname: Zhang
authors.forename: Kyoung-Jae
authors.initials: KJ
authors.lastname: Won
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D007438:Introns; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; D020033:Protein Isoforms; D014157:Transcription Factors; D008156:Luciferases