Zfp423 binds autoregulatory sites in p19 cell culture model

Autor: Kuixing Zhang, Chen-Jei Hong, Young-Wook Cho, Bruce A. Hamilton, Aiju Hou, Peter M. Gent, Kyoung-Jae Won
Rok vydání: 2012
Předmět:
lcsh:Medicine
Gene Expression
Biochemistry
Mice
Molecular cell biology
Genes
Reporter
Protein Isoforms
lcsh:Science
Luciferases
Zinc finger transcription factor
Genetics
Multidisciplinary
Gene Expression Regulation
Developmental
Cell Differentiation
Enhancer Elements
Genetic
Protein Binding
Signal Transduction
Research Article
Chromatin Immunoprecipitation
Immunoprecipitation
Molecular Sequence Data
DNA transcription
Biology
DNA-binding protein
Models
Biological
Molecular Genetics
Cell Line
Tumor
DNA-binding proteins
Animals
Humans
Gene Regulation
Gene Networks
Enhancer
Gene
Transcription factor
Binding Sites
lcsh:R
Intron
Proteins
Computational Biology
Sequence Analysis
DNA
Introns
Mutation
Genetics of Disease
lcsh:Q
Chromatin immunoprecipitation
Transcription Factors
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 6, p e66514 (2013)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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