Format

Send to

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

Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation.

Author information

1
Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
2
University of Freiburg, Faculty of Biology, Freiburg im Breisgau, Germany.
3
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
4
SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
5
The Francis Crick Institute, London, UK.
6
Stanford Genome Technology Center, Stanford University, Palo Alto, California, USA.
7
UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.

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.

PMID:
27183194
DOI:
10.1038/nsmb.3233
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center