Gene-specific modulation of TAF10 function by SET9-mediated methylation

Mol Cell. 2004 Apr 23;14(2):175-82. doi: 10.1016/s1097-2765(04)00182-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / metabolism
  • Baculoviridae / genetics
  • Binding Sites
  • Cell Line
  • Cell Nucleus / metabolism
  • Escherichia coli / genetics
  • Gene Expression Regulation
  • Genes, Reporter
  • Genetic Vectors
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Mutation
  • Nucleosomes / enzymology
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • RNA Polymerase II / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • TATA-Binding Protein Associated Factors / metabolism*
  • Time Factors
  • Transcription Factor TFIID / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Antibodies, Monoclonal
  • Histones
  • Nucleosomes
  • Proteins
  • Recombinant Fusion Proteins
  • TAF10 protein, human
  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • Methyltransferases
  • RNA Polymerase II
  • Lysine