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Chlamydas, S., Holz, H., Samata, M., Chelmicki, T., Georgiev, P., Pelechano, V., Dündar, F., Dasmeh, P., Mittler, G., Cadete, F.T., Ramírez, F., Conrad, T., Wei, W., Raja, S., Manke, T., Luscombe, N.M., Steinmetz, L.M., Akhtar, A. (2016). Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation.  Nat. Struct. Mol. Biol. 23(6): 580--589.
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Research paper

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.

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    Publication Type
    Nat. Struct. Mol. Biol.
    Nature Structural and Molecular Biology
    Publication Year
    1545-9993 1545-9985
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    Genes (21)
    Physical Interactions (7)
    Cell Lines (3)