The H3K4 Demethylase Lid Associates with and Inhibits Histone Deacetylase Rpd3

Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. .
Molecular and Cellular Biology (Impact Factor: 4.78). 03/2009; 29(6):1401-10. DOI: 10.1128/MCB.01643-08
Source: PubMed


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.

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Available from: Hediye Erdjument-Bromage, Apr 29, 2014
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    • "In this work, we analyze the contribution of dKDM5/LID to the regulation of the pattern of H3K4me3. Previous reports showed that dKDM5/LID is a component of various co-repressor complexes (32,33), which play a role in repression of NOTCH target genes (32,34). Similarly, several mammalian KDM5 isoforms associate with components of co-repressor complexes (35) and mediate repression (36–41). "
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