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Molecular and Cellular Biology, October 2006, p. 7224-7235, Vol. 26, No. 19
0270-7306/06/$08.00+0     doi:10.1128/MCB.00473-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Control of the DNA Methylation System Component MBD2 by Protein Arginine Methylation

Choon Ping Tan and Sara Nakielny*

Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, United Kingdom

Received 17 March 2006/ Returned for modification 13 April 2006/ Accepted 22 July 2006

DNA methylation is vital for proper chromatin structure and function in mammalian cells. Genetic removal of the enzymes that catalyze DNA methylation results in defective imprinting, transposon silencing, X chromosome dosage compensation, and genome stability. This epigenetic modification is interpreted by methyl-DNA binding domain (MBD) proteins. MBD proteins respond to methylated DNA by recruiting histone deacetylases (HDAC) and other transcription repression factors to the chromatin. The MBD2 protein is dispensable for animal viability, but it is implicated in the genesis of colon tumors. Here we report that the MBD2 protein is controlled by arginine methylation. We identify the protein arginine methyltransferase enzymes that catalyze this modification and show that arginine methylation inhibits the function of MBD2. Arginine methylation of MBD2 reduces MBD2-methyl-DNA complex formation, reduces MBD2-HDAC repression complex formation, and impairs the transcription repression function of MBD2 in cells. Our report provides a molecular description of a potential regulatory mechanism for an MBD protein family member. It is the first to demonstrate that protein arginine methyltransferases participate in the DNA methylation system of chromatin control.


* Corresponding author. Present address: Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205. Phone: (443) 287-7277. Fax: (410) 955-7407. E-mail: snakieln{at}jhsph.edu


Molecular and Cellular Biology, October 2006, p. 7224-7235, Vol. 26, No. 19
0270-7306/06/$08.00+0     doi:10.1128/MCB.00473-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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