p66[alpha]-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 18; p. 7487
• Main Authors: Gnanapragasam, Merlin Nithya, Scarsdale, J Neel, Amaya, Maria L, Webb, Heather D, Desai, Megha A, Walavalkar, Ninad M, Wang, Shou Zhen, Zhu, Sheng Zu, Ginder, Gordon D, Williams, David C
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 03.05.2011
• Subjects: Cells; Chromatin; DNA methylation; Epigenetics; Genes; Peptides
• ISSN: 0027-8424

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 coiled-coil interaction between MBD2 and p66α, a critical component of the MBD2-NuRD complex. We show that enforced expression of the isolated p66α 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 p66α 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. [PUBLICATION ABSTRACT]