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dc.contributor.authorHameed, Umar Farook Shahul
dc.contributor.authorLim, Jackwee
dc.contributor.authorZhang, Qian
dc.contributor.authorWasik, Mariusz A
dc.contributor.authorYang, Daiwen
dc.contributor.authorSwaminathan, Kunchithapadam
dc.date.accessioned2016-02-21T08:51:28Z
dc.date.available2016-02-21T08:51:28Z
dc.date.issued2014-05-09
dc.identifier.citationHameed UFS, Lim J, Zhang Q, Wasik MA, Yang D, et al. (2014) Transcriptional Repressor Domain of MBD1 is Intrinsically Disordered and Interacts with its Binding Partners in a Selective Manner. Scientific Reports 4. Available: http://dx.doi.org/10.1038/srep04896.
dc.identifier.issn2045-2322
dc.identifier.pmid24810720
dc.identifier.doi10.1038/srep04896
dc.identifier.urihttp://hdl.handle.net/10754/596829
dc.description.abstractMethylation 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.
dc.description.sponsorshipWe 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.
dc.publisherSpringer Nature
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.titleTranscriptional repressor domain of MBD1 is intrinsically disordered and interacts with its binding partners in a selective manner.
dc.typeArticle
dc.identifier.journalScientific Reports
dc.identifier.pmcidPMC4014985
dc.contributor.institution1] Department of Biological Sciences, National University of Singapore, Singapore 117543 [2].
dc.contributor.institutionDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
dc.contributor.institutionDepartment of Biological Sciences, National University of Singapore, Singapore 117543.
refterms.dateFOA2018-06-13T14:20:44Z
dc.date.published-online2014-05-09
dc.date.published-print2015-05


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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit
Except where otherwise noted, this item's license is described as This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit