PMID- 11909860 OWN - NLM STAT- MEDLINE DCOM- 20020702 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 22 DP - 2002 May 31 TI - The viral transactivator E1A regulates the mouse mammary tumor virus promoter in an isoform- and chromatin-specific manner. PG - 19847-54 AB - Proteins encoded by the adenovirus E1A gene regulate both cellular and viral genes to mediate effects on cell cycle, differentiation, and cell growth control. We have identified the mouse mammary tumor virus (MMTV) promoter as a target of E1A action and investigated the role nucleoprotein structure plays in its response to E1A. Both 12 and 13 S forms target the MMTV promoter when it has a disorganized and accessible chromatin configuration. However, whereas the 13 S form is stimulatory, the 12 S form is repressive. When the MMTV promoter adopts an organized and repressed chromatin structure, it is targeted only by the 13 S form, which stimulates it. Although evidence indicates that E1A interacts with the SWI/SNF remodeling complex, E1A had no effect on chromatin remodeling at the MMTV promoter in organized chromatin. Analysis of E1A mutants showed that stimulation of the MMTV promoter is mediated solely through conserved region 3 and does not require interaction with Rb, p300/CBP-associated factor, or CBP/p300. Imaging analysis showed that E1A colocalizes with MMTV sequences in vivo, suggesting that it functions directly at the promoter. These results indicate that E1A stimulates the MMTV promoter in a fashion independent of chromatin conformation and through a direct mechanism involving interaction with the basal transcription machinery. FAU - Soeth, Edlyn AU - Soeth E AD - Signal Transduction Group, Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Thurber, Denise B AU - Thurber DB FAU - Smith, Catharine L AU - Smith CL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020321 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Adenovirus E1A Proteins) RN - 0 (Chromatin) RN - 0 (Protein Isoforms) RN - 63231-63-0 (RNA) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Adenovirus E1A Proteins/*metabolism/*physiology MH - Animals MH - Cell Line MH - Cell Nucleus/metabolism MH - Chromatin/metabolism MH - Fluorescent Antibody Technique, Indirect MH - Genetic Vectors MH - Luciferases/metabolism MH - Mammary Tumor Virus, Mouse/*genetics MH - Mice MH - Microscopy, Fluorescence MH - Mutation MH - Plasmids/metabolism MH - *Promoter Regions, Genetic MH - Protein Binding MH - Protein Isoforms MH - RNA/metabolism MH - Transcription, Genetic MH - Transfection MH - Tumor Cells, Cultured EDAT- 2002/03/23 10:00 MHDA- 2002/07/03 10:01 CRDT- 2002/03/23 10:00 PHST- 2002/03/23 10:00 [pubmed] PHST- 2002/07/03 10:01 [medline] PHST- 2002/03/23 10:00 [entrez] AID - S0021-9258(20)85053-4 [pii] AID - 10.1074/jbc.M200629200 [doi] PST - ppublish SO - J Biol Chem. 2002 May 31;277(22):19847-54. doi: 10.1074/jbc.M200629200. Epub 2002 Mar 21.