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Solution structure of the coiled-coil complex between MBD2 and p66alphaSolution structure of the coiled-coil complex between MBD2 and p66alpha
Structural highlights
Function[P66A_HUMAN] Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B.[1] [2] Publication Abstract from PubMedNucleosome 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 beta-type globin gene silencing during development in vivo. Here we present structural and biophysical details of the coiled-coil interaction between MBD2 and p66alpha, a critical component of the MBD2-NuRD complex. We show that enforced expression of the isolated p66alpha 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 p66alpha 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. p66{alpha}-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.,Gnanapragasam MN, Scarsdale JN, Amaya ML, Webb HD, Desai MA, Walavalkar NM, Wang SZ, Zhu SZ, Ginder GD, Williams DC Jr Proc Natl Acad Sci U S A. 2011 Apr 13. PMID:21490301[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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