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  • Mutation  (2)
  • (Rat liver)
  • 550 - Earth sciences
  • Molecular Sequence Data
  • American Association for the Advancement of Science (AAAS)  (2)
  • 2005-2009  (2)
  • 1
    Publication Date: 2008-08-23
    Description: Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756290/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756290/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Horwitz, Gregory A -- Zhang, Kangling -- McBrian, Matthew A -- Grunstein, Michael -- Kurdistani, Siavash K -- Berk, Arnold J -- CA25235/CA/NCI NIH HHS/ -- R37 CA025235/CA/NCI NIH HHS/ -- R37 CA025235-30/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1084-5. doi: 10.1126/science.1155544.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719283" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Adenovirus E1A Proteins/genetics/*metabolism ; Adenoviruses, Human/*metabolism ; Antigens, Polyomavirus Transforming/metabolism ; CREB-Binding Protein/metabolism ; *Cell Cycle ; Cell Line ; Cell Transformation, Viral ; Cells, Cultured ; HeLa Cells ; Histones/*metabolism ; Humans ; Lysine/metabolism ; Mutation ; p300-CBP Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2008-08-23
    Description: Adenovirus e1a induces quiescent human cells to replicate. We found that e1a causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and p107) and p300/CBP histone acetyltransferases on promoters, the effect of which is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set of genes, thereby stimulating cell cycling and inhibiting antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to promoters of cell cycle and growth genes, causing enrichment of p300/CBP, PCAF (p300/CBP-associated factor), and H3K18ac; depletion of RB proteins; and transcriptional activation. e1a also associates transiently with promoters of antiviral genes, causing enrichment for RB, p130, and H4K16ac; increased nucleosome density; and transcriptional repression. At later times, e1a and p107 bind mainly to promoters of development and differentiation genes, repressing transcription. The temporal order of e1a binding requires its interactions with p300/CBP and RB proteins. Our data uncover a defined epigenetic reprogramming leading to cellular transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693122/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693122/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferrari, Roberto -- Pellegrini, Matteo -- Horwitz, Gregory A -- Xie, Wei -- Berk, Arnold J -- Kurdistani, Siavash K -- CA25235/CA/NCI NIH HHS/ -- R37 CA025235/CA/NCI NIH HHS/ -- R37 CA025235-30/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1086-8. doi: 10.1126/science.1155546.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719284" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/genetics/*metabolism ; Adenoviruses, Human/genetics/*metabolism ; CREB-Binding Protein/metabolism ; Cell Transformation, Viral ; Crk-Associated Substrate Protein/genetics/metabolism ; *Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation ; Histones/metabolism ; Humans ; Mutation ; Promoter Regions, Genetic ; Protein Binding ; RNA, Messenger/genetics/metabolism ; Retinoblastoma Protein/genetics/metabolism ; Retinoblastoma-Like Protein p107/genetics/metabolism ; Transcription, Genetic ; p300-CBP Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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