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Edited by Jasper Rine, University of California, Berkeley, CA, and approved February 10, 2009
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↵1P.-O.E. and H.G.C. contributed equally to this work. (received for review October 15, 2008)
Abstract
Inheritance of epigenetic information encoded by cytosine DNA methylation patterns is crucial for mammalian cell survival, in large part through the activity of the maintenance DNA methyltransferase (DNMT1). Here, we show that SET7, a known histone methyltransferase, is involved in the regulation of protein stability of DNMT1. SET7 colocalizes and directly interacts with DNMT1 and specifically monomethylates Lys-142 of DNMT1. Methylated DNMT1 peaks during the S and G2 phases of the cell cycle and is prone to proteasome-mediated degradation. Overexpression of SET7 leads to decreased DNMT1 levels, and siRNA-mediated knockdown of SET7 stabilizes DNMT1. These results demonstrate that signaling through SET7 represents a means of DNMT1 enzyme turnover.
Footnotes
- 2To whom correspondence should be addressed. E-mail: pradhan{at}neb.com
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Author contributions: G.A.H., S.E.J., and S.P. designed research; P.-O.E., H.G.C., J.B., G.R.F., and M.S. performed research; P.-O.E. and S.P. analyzed data; and S.E.J. and S.P. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0810362106/DCSupplemental.
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Freely available online through the PNAS open access option.
Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells
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