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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ginder, Gordon D. Wang, Shou Zhen Scarsdale, J. Neel Amaya, Maria L. Williams, David C. Desai, Megha A. Gnanapragasam, Merlin Nithya Zu Zhu, Sheng Walavalkar, Ninad M. Webb, Heather D. |
| Description | Author Affiliation: Gnanapragasam MN ( Department of Human and Molecular Genetics, Institute of Structural Biology and Drug Design, Center for the Study of Biological Complexity, and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.); |
| Abstract | Nucleosome remodeling complexes comprise several large families of chromatin modifiers that integrate multiple epigenetic control signals to play key roles in cell type-specific transcription regulation. We previously isolated a methyl-binding domain protein 2 (MBD2)-containing nucleosome remodeling and deacetylation (NuRD) complex from primary erythroid cells and showed that MBD2 contributes to DNA methylation-dependent embryonic and fetal ß-type globin gene silencing during development in vivo. Here we present structural and biophysical details of the coiled-coil interaction between MBD2 and p66 , a critical component of the MBD2-NuRD complex. We show that enforced expression of the isolated p66 coiled-coil domain relieves MBD2-mediated globin gene silencing and that the expressed peptide interacts only with a subset of components of the MBD2-NuRD complex that does not include native p66 or Mi-2. These results demonstrate the central importance of the coiled-coil interaction and suggest that MBD2-dependent DNA methylation-driven gene silencing can be disrupted by selectively targeting this coiled-coil complex. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 18 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA-Binding Proteins Metabolism Epigenesis, Genetic Genetics Mi-2 Nucleosome Remodeling And Deacetylase Complex Models, Molecular Repressor Proteins Blotting, Western DNA Methylation DNA Primers Gene Silencing Immunoprecipitation RNA Interference Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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