title: Transcriptional regulation by Barhl1 and Brn-3c in organ-of-Corti-derived cell lines.
abstract: Barhl1 and Brn-3c have been identified as transcription factors that are essential for survival and maintenance of hair cells of the inner ear. Little is known about the mechanism of how Brn-3c or Barhl1 may regulate transcription in the inner ear. In this study, the transcriptional function of both Brn-3c and Barhl1 was investigated in the organ-of-Corti-derived cell lines, OC-1 and OC-2. We examined regulatory domains in these transcription factors by linking regions of Barhl1 and Brn-3c to the DNA binding domain of the heterologous transcription factor GAL4 and assayed their effect on a heterologous promoter containing GAL4 DNA binding sites by co-transfection into OC-1 and OC-2 cell lines. Brn-3c was found to contain an independent N-terminal activation domain that is sufficient to activate gene transcription in the organ of corti derived cell lines. Barhl1 on the other hand was found to act as a transcriptional repressor with repressive activity not restricted to a particular domain of Barhl1. In addition, we analyzed the effect of Barhl1 on the promoters of the neurotrophin genes NT-3 and BDNF in OC-1 and OC-2 cell lines. However, Barhl1 was not found to directly regulate neurotrophin promoter constructs in these cells.
authors.affiliation: Molecular Audiology Group, Centre for Auditory Research, UCL Ear Institute, 332 Gray's Inn Rd, London WC1X 8EE, UK.
authors.forename: Richa
authors.initials: R
authors.lastname: Sud
authors.forename: Chris M
authors.initials: CM
authors.lastname: Jones
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Dawson
mesh_terms: D000818:Animals; D001665:Binding Sites; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D005813:Genes, Synthetic; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000235:genetics*; D009925:Organ of Corti / Q000166:cytology*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050821:Transcription Factor Brn-3C / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection
chemical_list: C485866:Barhl1 protein, mouse; D019208:Brain-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; C121290:Pou4f3 protein, mouse; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D050821:Transcription Factor Brn-3C