title: Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.
abstract: Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-&#946;, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication.
authors.affiliation: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Gou
authors.affiliation: Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Gauri
authors.initials: G
authors.lastname: Jawdekar
authors.affiliation: Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Nava
authors.affiliation: Department of Biological Chemistry, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Trent
authors.initials: T
authors.lastname: Su
authors.affiliation: Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Yousef
authors.affiliation: Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Zemke
authors.affiliation: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Molecular, Cellular, and Developmental Biology, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Biological Chemistry, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Pathology and Laboratory of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA.
authors.forename: Siavash K
authors.initials: SK
authors.lastname: Kurdistani
authors.affiliation: Molecular Biology Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA; Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1570, USA. Electronic address: berk@mbi.ucla.edu.
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Berk
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D014779:Virus Replication; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: D017500:Adenovirus E1A Proteins; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D002843:Chromatin; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D050880:p300-CBP Transcription Factors