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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Frye, Roy A. Senawong, Thanaset Shepherd, David M. Leid, Mark Minucci, Saverio Peterson, Valerie J. Avram, Dorina |
| Description | Author Affiliation: Senawong T ( Laboratory of Molecular Pharmacology, Department of Pharmaceutical Sciences, College of Pharmacy, Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon 97331, USA.) |
| Abstract | Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting proteins 1 and 2 (CTIP1 and CTIP2) enhance transcriptional repression mediated by COUP-TF II and have been implicated in hematopoietic cell development and malignancies. CTIP1 and CTIP2 are also sequence-specific DNA-binding proteins that repress transcription through direct, COUP-TF-in-dependent binding to a GC-rich response element. CTIP1- and CTIP2-mediated transcriptional repression is insensitive to trichostatin A, an inhibitor of known class I and II histone deacetylases. However, chromatin immunoprecipitation assays revealed that expression of CTIP2 in mammalian cells resulted in deacetylation of histones H3 and/or H4 that were associated with the promoter region of a reporter gene. CTIP2-mediated transcriptional repression, as well as deacetylation of promoter-associated histones H3/H4 in CTIP2-transfected cells, was reversed by nicotinamide, an inhibitor of class III histone deacetylases such as the mammalian homologs of yeast Silent Information Regulator 2 (Sir2). The human homolog of yeast Sir2, SIRT1, was found to interact directly with CTIP2 and was recruited to the promoter template in a CTIP2-dependent manner. Moreover, SIRT1 enhanced the deacetylation of template-associated histones H3/H4 in CTIP2-transfected cells, and stimulated CTIP2-dependent transcriptional repression. Finally, endogenous SIRT1 and CTIP2 co-purified from Jurkat cell nuclear extracts in the context of a large (1-2 mDa) complex. These findings implicate SIRT1 as a histone H3/H4 deacetylase in mammalian cells and in transcriptional repression mediated by CTIP2. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 44 |
| Volume Number | 278 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2003-10-31 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carrier Proteins DNA-Binding Proteins Metabolism Physiology Histone Deacetylases Nuclear Proteins Receptors, Steroid Repressor Proteins Sirtuins Transcription Factors COUP Transcription Factors Cell Line Cell Nucleus Chromatin DNA Chemistry Enzyme Inhibitors Pharmacology Gene Silencing Genes, Reporter Glutathione Transferase Hydroxamic Acids Immunoblotting Jurkat Cells NAD Neoplasm Proteins Niacinamide Precipitin Tests Protein Binding Recombinant Fusion Proteins Sirtuin 1 Transcription, Genetic Transfection Tumor Suppressor Proteins Research Support, U.S. Gov't, P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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