Functional Interplay Between MSL1 and CDK7 Controls RNA Polymerase II Ser5 Phosphorylation

Nat Struct Mol Biol. 2016 Jun;23(6):580-9. doi: 10.1038/nsmb.3233. Epub 2016 May 16.

Abstract

Proper gene expression requires coordinated interplay among transcriptional coactivators, transcription factors and the general transcription machinery. We report here that MSL1, a central component of the dosage compensation complex in Drosophila melanogaster and Drosophila virilis, displays evolutionarily conserved sex-independent binding to promoters. Genetic and biochemical analyses reveal a functional interaction of MSL1 with CDK7, a subunit of the Cdk-activating kinase (CAK) complex of the general transcription factor TFIIH. Importantly, MSL1 depletion leads to decreased phosphorylation of Ser5 of RNA polymerase II. In addition, we demonstrate that MSL1 is a phosphoprotein, and transgenic flies expressing MSL1 phosphomutants show mislocalization of the histone acetyltransferase MOF and histone H4 K16 acetylation, thus ultimately causing male lethality due to a failure of dosage compensation. We propose that, by virtue of its interaction with components of the general transcription machinery, MSL1 exists in different phosphorylation states, thereby modulating transcription in flies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Chromatin / genetics
  • Chromatin / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Dosage Compensation, Genetic
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Female
  • Gene Deletion
  • Male
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Polymerase II / metabolism*
  • Serine / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • Chromatin
  • Drosophila Proteins
  • Nuclear Proteins
  • Transcription Factors
  • msl-1 protein, Drosophila
  • Serine
  • Cyclin-Dependent Kinases
  • cyclin-dependent kinase-activating kinase
  • RNA Polymerase II