title: CTIP2 associates with the NuRD complex on the promoter of p57KIP2, a newly identified CTIP2 target gene.
abstract: Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2 (CTIP2), also known as Bcl11b, is a transcriptional repressor that functions by direct, sequence-specific DNA binding activity or by recruitment to the promoter template by interaction with COUP-TF family members. CTIP2 is essential for both T cell development and axonal projections of corticospinal motor neurons in the central nervous system. However, little is known regarding the molecular mechanism(s) by which CTIP2 contributes to either process. CTIP2 complexes that were isolated from SK-N-MC neuroblastoma cells were found to harbor substantial histone deacetylase activity, which was likely conferred by the nucleosome remodeling and deacetylation (NuRD) complex. CTIP2 was found to associate with the NuRD complex through direct interaction with both RbAp46 and RbAp48, and components of the NuRD complex were found to be recruited to an artificial promoter template in a CTIP2-dependent manner in transfected cells. Finally, the NuRD complex and CTIP2 were found to co-occupy the promoter template of p57KIP2, a gene encoding a cyclin-dependent kinase inhibitor, and identified herein as a novel transcriptional target of CTIP2 in SK-N-MC cells. Therefore, it seems likely that the NuRD complex may be involved in transcriptional repression of CTIP2 target genes and contribute to the function(s) of CTIP2 within a neuronal context.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Acharawan
authors.initials: A
authors.lastname: Topark-Ngarm
authors.forename: Olga
authors.initials: O
authors.lastname: Golonzhka
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Peterson
authors.forename: Brian
authors.initials: B
authors.lastname: Barrett
authors.forename: Brigetta
authors.initials: B
authors.lastname: Martinez
authors.forename: Kristi
authors.initials: K
authors.lastname: Crofoot
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Filtz
authors.forename: Mark
authors.initials: M
authors.lastname: Leid
mesh_terms: D001665:Binding Sites; D051837:COUP Transcription Factor II / Q000235:genetics* / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D051837:COUP Transcription Factor II; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D011993:Recombinant Fusion Proteins; C012589:trichostatin A; D008156:Luciferases; D005982:Glutathione Transferase; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex