E1A is the component of the MHC class I enhancer complex that mediates HDAC chromatin repression in adenovirus-12 tumorigenic cells.
In adenovirus-12 tumorigenic cells, the viral E1A-12 protein mediates transcriptional down-regulation of the major histocompatibility complex (MHC) class I genes by targeting the class I enhancer. Here, we demonstrate by a combination of antisense and chromatin immunoprecipitation (ChIP) analysis that E1A-12 is a physical component of the class I enhancer repression complex, known to comprise COUP-TFII and histone deacetylase 1 (HDAC1). Significantly, E1A antisense was shown to co-eliminate E1A-12 as well as HDAC1 and HDAC8, but not HDAC3, from the enhancer repression complex. Consistent with elimination of HDAC1 and HDAC8, E1A antisense also resulted in a dramatic increase in histone acetylation, a hallmark of transcriptionally active chromatin. Importantly, MHC class I antigen expression was restored on the surface of E1A antisense-transfected cells. These results demonstrate that E1A-12 is associated with the MHC class I complex and apparently mediates class I transcriptional down-regulation by enacting chromatin repression through HDAC1 and HDAC8.
Zhao
Biwei
B
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Levy Research Building, Room 221, 4010 Locust Street, Philadelphia, PA 19104, USA.
Ricciardi
Robert P
RP
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics*; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics
D017500:Adenovirus E1A Proteins; D002843:Chromatin; D015395:Histocompatibility Antigens Class I; D020319:Oligodeoxyribonucleotides, Antisense; D006655:Histone Deacetylases