Article

SET7/9 mediated methylation of non-histone proteins in mammalian cells

New England Biolabs Inc, Ipswich, MA, USA.
Epigenetics: official journal of the DNA Methylation Society (Impact Factor: 4.78). 09/2009; 4(6):383-7. DOI: 10.4161/epi.4.6.9450
Source: PubMed

ABSTRACT

Lysine methylation has emerged as a major posttranslational modification for histones in eukaryotes. Crosstalk between lysine methylation and other posttranslational modifications is crucial for transcriptional gene regulation and epigenetic inheritance. In addition to histones, several other cellular proteins including transcription factors, tumor suppressor and membrane-associated receptors are subject to lysine methylation. SET7/9 plays a prominent role in lysine methylation of histone and non-histone proteins. Recent reports have suggested a new mechanism of epigenetic gene regulation via SET7/9 modulated DNMT1 methylation. In this mechanism, SET7/9 may methylate DNMT1 leading to proteasome mediated protein degradation, and antagonist lysine specific demethylase (LSD), may prevent this degradation by removing the methyl mark. Thus a fine-tuning and balance between cellular SET7/9 and LSD interaction with DNMT1 may be means for epigenetic gene regulation.

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    • "Set7 is a KMT that was initially identified as a monomethylase of histone H3 lysine 4 (H3K4) in vitro (Wang et al., 2001). However , because Set7 is unable to methylate nucleosomes at H3K4 (Chuikov et al., 2004) and Setd7 À/À mouse embryonic fibroblasts (MEFs) have normal levels of H3K4 methylation (Lehnertz et al., 2011), it is more likely that the primary role for Set7 is methylation of nonhistone substrates (Pradhan et al., 2009). Indeed, Set7 has been shown to methylate and alter function of a wide variety of proteins including Dnmt1, Taf10, p53, Stat3, and NF-kB in vitro (Chuikov et al., 2004; Ea and Baltimore, 2009; Estè ve et al., 2009; Kouskouti et al., 2004; Kurash et al., 2008; Yang et al., 2009, 2010a, 2010b). "
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    • "HKMT7 contains only one protein, Set7/9, which monomethylates histone at H3-K4 [68]. Set7/9 methylates also non-histone proteins, including p53, DNA methyltransferase 1 (DNMT1), nuclear factor kappa B (NFkB) and nuclear hormone estrogen receptor alpha (ER) [59]. HKMT8 includes only one member, RIZ1. "
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