Gene-specific modulation of TAF10 function by SET9-mediated methylation.
SET9 is a member of the SET domain-containing histone methyltransferase family that can specifically methylate histone 3 at lysine 4 position. Although nucleosomal histones are poor substrates for SET9, the active enzyme can stimulate activator-induced transcription. Here, we show that SET9 can monomethylate the TBP-associated factor TAF10 at a single lysine residue located at the loop 2 region within the putative histone-fold domain of the protein. Methylated TAF10 has an increased affinity for RNA polymerase II, pointing to a direct role of this modification in preinitiation complex formation. Reporter assays and studies on TAF10 null F9 cells expressing a methylation-deficient TAF10 mutant revealed that SET9-mediated methylation of TAF10 potentiates transcription of some but not all TAF10-dependent genes. This gene specificity correlated with SET9 recruitment. The promoter-specific effects of SET9-methylated TAF10 may have important implications regarding the biological function of SET domain-containing lysine methylases, whose primary targets have been presumed to be histones.
Kouskouti
Antigone
A
Institute of Molecular Biology and Biotechnology, FORTH, 711 10 Herakleion, Crete, Greece.
Scheer
Elisabeth
E
Staub
Adrien
A
Tora
Làszlò
L
Talianidis
Iannis
I
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009707:Nucleosomes / Q000201:enzymology; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D013997:Time Factors; D035362:Transcription Factor TFIID / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D000911:Antibodies, Monoclonal; D006657:Histones; D009707:Nucleosomes; D011506:Proteins; D011993:Recombinant Fusion Proteins; C089768:TAF10 protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D008780:Methyltransferases; D012319:RNA Polymerase II; D008239:Lysine