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Molecular and Cellular Biology, February 2006, p. 843-851, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.843-851.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

MBD2/NuRD and MBD3/NuRD, Two Distinct Complexes with Different Biochemical and Functional Properties

Xavier Le Guezennec,1,{dagger} Michiel Vermeulen,1,{dagger} Arie B. Brinkman,1 Wieteke A. M. Hoeijmakers,1 Adrian Cohen,1 Edwin Lasonder,1,2 and Hendrik G. Stunnenberg1*

Department of Molecular Biology, Nijmegen Center for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands,1 Center for Molecular and Biomolecular Informatics, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands2

Received 20 August 2005/ Returned for modification 18 September 2005/ Accepted 16 November 2005

The human genome contains a number of methyl CpG binding proteins that translate DNA methylation into a physiological response. To gain insight into the function of MBD2 and MBD3, we first applied protein tagging and mass spectrometry. We show that MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like complexes, called MBD2/NuRD and MBD3/NuRD. We identified DOC-1, a putative tumor suppressor, as a novel core subunit of MBD2/NuRD as well as MBD3/NuRD. PRMT5 and its cofactor MEP50 were identified as specific MBD2/NuRD interactors. PRMT5 stably and specifically associates with and methylates the RG-rich N terminus of MBD2. Chromatin immunoprecipitation experiments revealed that PRMT5 and MBD2 are recruited to CpG islands in a methylation-dependent manner in vivo and that H4R3, a substrate of PRMT, is methylated at these loci. Our data show that MBD2/NuRD and MBD3/NuRD are distinct protein complexes with different biochemical and functional properties.

* Corresponding author. Mailing address: Department of Molecular Biology, NCMLS M850/3.79, Radboud University, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31-24-3610524. Fax: 31-24-3610520. E-mail: h.stunnenberg{at}ncmls.ru.nl.

{dagger} The first two authors contributed equally.

Molecular and Cellular Biology, February 2006, p. 843-851, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.843-851.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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