hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes.
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.
Tanaka
Tomoaki
T
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Ohkubo
Shuichi
S
Tatsuno
Ichiro
I
Prives
Carol
C
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*
D029563:Cellular Apoptosis Susceptibility Protein; D002843:Chromatin; D006657:Histones; D016159:Tumor Suppressor Protein p53