title: The H3K4 demethylase lid associates with and inhibits histone deacetylase Rpd3.
abstract: JmjC domain-containing proteins have been shown to possess histone demethylase activity. One of these proteins is the Drosophila histone H3 lysine 4 demethylase Little imaginal discs (Lid), which has been genetically classified as a Trithorax group protein. However, contrary to the supposed function of Lid in gene activation, the biochemical activity of this protein entails the removal of a histone mark that is correlated with active transcription. To understand the molecular mechanism behind the function of Lid, we have purified a Lid-containing protein complex from Drosophila embryo nuclear extracts. In addition to Lid, the complex contains Rpd3, CG3815/Drosophila Pf1, CG13367, and Mrg15. Rpd3 is a histone deacetylase, and along with Polycomb group proteins, which antagonize the function of Trithorax group proteins, it negatively regulates transcription. By reconstituting the Lid complex, we demonstrated that the demethylase activity of Lid is not affected by its association with other proteins. However, the deacetylase activity of Rpd3 is greatly diminished upon incorporation into the Lid complex. Thus, our finding that Lid antagonizes Rpd3 function provides an explanation for the genetic classification of Lid as a positive transcription regulator.
authors.affiliation: Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. yi_zhang@med.unc.edu.
authors.forename: Nara
authors.initials: N
authors.lastname: Lee
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Richard S
authors.initials: RS
authors.lastname: Jones
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002457:Cell Extracts; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002457:Cell Extracts; D029721:Drosophila Proteins; D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D056466:Histone Demethylases; C518655:Lid protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases