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SET 7/9

SET7/9 is a mammalian specific histone lysine methyltransferases. It was identified as methylating H3 Lys4 in vitro using labeled S-adenosyl-L-methionine. In vivo, an antibody to methylated H3 Lys4 recognized only H3 in purified 293T cells. SET7/9 does not contain the upstream and downstream cysteine regions required for lysine HMTase activity in the SU(VAR)3-9 homologues. The regions are therefore not required for a SET domain protein to have lysine HMTase activity. In fact, all the S. cerevisiae SET domain lysine HMTases are lacking the cystein regions. Deletion of the SET7/9 upstream and downstream sequences does eliminate its HMTase activity (Wang et al 2001b).

Methylation of Lys4 by Set7/9 is associated with transcription activation. Methylation by Set7/9 inhibits methylation of Lys9 by SUV39H1 and vice versa (Wang et al 2001b). Methylation of Lys4 enhances acetylation of H4 by p300. Methylation of Lys4 prevents the association of the NuRD? complex with the H3 tail. NuRD? contains two histone deacetylaces, HDAC1 and HDAC2, and is associated with transcription repression.

(Caitlin Reavey)

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