title: Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation.
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.
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Sarantis
authors.initials: S
authors.lastname: Chlamydas
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Holz
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.|University of Freiburg, Faculty of Biology, Freiburg im Breisgau, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Samata
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Chelmicki
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Plamen
authors.initials: P
authors.lastname: Georgiev
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.|SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
authors.forename: Vicent
authors.initials: V
authors.lastname: Pelechano
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.|University of Freiburg, Faculty of Biology, Freiburg im Breisgau, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Dündar
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Pouria
authors.initials: P
authors.lastname: Dasmeh
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mittler
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Filipe Tavares
authors.initials: FT
authors.lastname: Cadete
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Fidel
authors.initials: F
authors.lastname: Ramírez
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Conrad
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.|Stanford Genome Technology Center, Stanford University, Palo Alto, California, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Wei
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Sunil
authors.initials: S
authors.lastname: Raja
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.affiliation: The Francis Crick Institute, London, UK.|UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.|Stanford Genome Technology Center, Stanford University, Palo Alto, California, USA.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Asifa
authors.initials: A
authors.lastname: Akhtar
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; D012694:Serine; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722436:Cdk7 protein, Drosophila