Transcriptional repressor domain of MBD1 is intrinsically disordered and interacts with its binding partners in a selective manner.

Umar Farook Shahul Hameed, Jackwee Lim, Qian Zhang, Mariusz A Wasik, Daiwen Yang, Kunchithapadam Swaminathan

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11 Scopus citations


Methylation of DNA CpG sites is a major mechanism of epigenetic gene silencing and plays important roles in cell division, development and carcinogenesis. One of its regulators is the 64-residue C-terminal Transcriptional Repressor Domain (the TRD) of MBD1, which recruits several repressor proteins such as MCAF1, HDAC3 and MPG that are essential for the gene silencing. Using NMR spectroscopy, we have characterized the solution structure of the C-terminus of MBD1 (MBD1-c, residues D507 to Q605), which included the TRD (A529 to P592). Surprisingly, the MBD1-c is intrinsically disordered. Despite its lack of a tertiary folding, MBD1-c could still bind to different partner proteins in a selective manner. MPG and MCAF1Δ8 showed binding to both the N-terminal and C-terminal residues of MBD1-c but HDAC3 preferably bound to the C-terminal region. This study reveals how MBD1-c discriminates different binding partners, and thus, expands our understanding of the mechanisms of gene regulation by MBD1.
Original languageEnglish (US)
JournalScientific Reports
Issue number1
StatePublished - May 9 2014
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We appreciate the support of Profs. Rabindra Roy from Georgetown University, USA and Luciano DiCroce from Center for Genomic Regulation, Spain for providing the MPG and HDAC3 expression constructs, respectively. The authors thank the BioScience core Lab of King Abdullah University of Science and Technology (KAUST), Saudi Arabia for their support in performing ITC experiments. This project was supported by Academic Research Fund (FRC) of the Ministry of Education, Singapore to K.S. and National University of Singapore research scholarship to U.F.S.H.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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