title: ΔNp63α utilizes multiple mechanisms to repress transcription in squamous cell carcinoma cells.
abstract: ΔNp63α is a potent oncogene in squamous cell carcinomas (SCCs) and a pro-proliferative factor expressed by basal epithelial cells. ΔNp63α functions both as a transcriptional repressor and activator, but it is not clear how these activities contribute to its oncogenic potential. ΔNp63α was proposed to function as a dominant negative of the related factor p53. Additionally, ΔNp63α was shown to inactivate its family member TAp73 and mediate recruitment of repressive histone deacetylase (HDAC) complexes to chromatin. Recently, we identified a new mechanism of repression involving recruitment of histone H2A/H2A.Z exchange complexes and H2A.Z deposition at ΔNp63α target genes. Here, we aimed to define the possible co-occurrence of the various repressive mechanisms. In lung SCC cells expressing ΔNp63α, p53 and TAp73, we found that ΔNp63α exerts its pro-proliferative and transcriptional repressive effects in a manner independent of p53, TAp73 and histone H3 and H4 deacetylation. Instead, ΔNp63α target genes are differentiated from non-target genes within the p53 network by incorporation and accumulation of acetylated H2A.Z. These results indicate that ΔNp63α utilizes multiple mechanisms of repression in diverse epithelial and SCC cells.
authors: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO, USA.
authors: Corrie L
authors: CL
authors: Gallant-Behm
authors: Joaquín M
authors: JM
authors: Espinosa
mesh_terms: D000107:Acetylation; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C115051:TP63 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D006655:Histone Deacetylases
keywords: H2A.Z; histone acetylation; oncogene; p53; p73; squamous cell carcinoma; transcriptional repression