p66α—MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2—NuRD complex

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...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 108; no. 18; pp. 7487 - 7492
Main Authors Gnanapragasam, Merlin Nithya, Scarsdale, J. Neel, Amaya, Maria L., Webb, Heather D., Desai, Megha A., Walavalkar, Ninad M., Wang, Shou Zhen, Zu Zhu, Sheng, Ginder, Gordon D., Williams, David C., Felsenfeld, Gary
Format Journal Article
LanguageEnglish
Published National Academy of Sciences 03.05.2011
National Acad Sciences
Subjects
Biological Sciences
Cellular immunity
Chromatin
Deacetylation
Development
Directional control
DNA
DNA methylation
Embryogenesis
epigenetics
Erythroid cells
Fetuses
Gene expression
Gene silencing
Genes
Histone deacetylase
Methylation
Nucleosomes
NuRD protein
Proteins
Transcription
Transgenic animals
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Summary: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 β-type globin gene silencing during development in vivo. Here we present structural and biophysical details of the coiledcoil interaction between MBD2 and p66α, a critical component of the MBD2-NuRD complex. We show that enforced expression of the isolated 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 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.
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SourceType-Scholarly Journals-1
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Edited* by Gary Felsenfeld, National Institutes of Health, Bethesda, MD, and approved March 16, 2011 (received for review October 12, 2010)
Author contributions: M.N.G., G.D.G., and D.C.W. designed research; M.N.G., J.N.S., M.L.A., H.D.W., M.A.D., N.M.W., S.Z.W., S.Z.Z., and D.C.W. performed research; M.N.G., G.D.G., and D.C.W. analyzed data; and M.N.G., G.D.G., and D.C.W. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1015341108