title: hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes.
abstract: The p53 tumor suppressor protein regulates many genes that can determine different cellular outcomes such as growth arrest or cell death. Promoter-selective transactivation by p53, although critical for the different cellular outcomes, is not well understood. We report here that the human cellular apoptosis susceptibility protein (hCAS/CSE1L) associates with a subset of p53 target promoters, including PIG3, in a p53-autonomous manner. Downregulation of hCAS/CSE1L decreases transcription from those p53 target promoters to which it preferentially binds and reduces apoptosis. In addition, hCAS/CSE1L silencing leads to increased methylation of histone H3 lysine 27 within the PIG3 gene. hCAS/CSE1L was previously shown to function as a nucleo-cytoplasmic transport factor, as does its closely related yeast homologue Cse1, which can also associate with chromatin and serve as a barrier protein that prevents spreading of heterochromatin. Thus, human CAS/CSE1L can bind select genes with significant functional consequences for p53-mediated transcription and determine cellular outcome.
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Tomoaki
authors: T
authors: Tanaka
authors: Shuichi
authors: S
authors: Ohkubo
authors: Ichiro
authors: I
authors: Tatsuno
authors: Carol
authors: C
authors: Prives
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000473:pathology; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D029563:Cellular Apoptosis Susceptibility Protein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein; D002843:Chromatin; D006657:Histones; D016159:Tumor Suppressor Protein p53