The MLE subunit of the Drosophila MSL complex uses its ATPase activity for dosage compensation and its helicase activity for targeting.
In Drosophila, dosage compensation-the equalization of most X-linked gene products between XY males and XX females-is mediated by the MSL complex that preferentially associates with numerous sites on the X chromosome in somatic cells of males, but not of females. The complex consists of a noncoding RNA and a core of five protein subunits that includes a histone acetyltransferase (MOF) and an ATP-dependent DEXH box RNA/DNA helicase (MLE). Both of these enzymatic activities are necessary for the spreading of the complex to its sites of action along the X chromosome. MLE is related to the ATPases present in complexes that remodel chromatin by altering the positioning or the architectural relationship between nucleosomes and DNA. In contrast to MLE, none of these enzymatic subunits has been shown to possess double-stranded nucleic acid-unwinding activity. We investigated the function of MLE in the process of dosage compensation by generating mutations that separate ATPase activity from duplex unwinding. We show that the ATPase activity is sufficient for MLE's role in transcriptional enhancement, while the helicase activity is necessary for the spreading of the complex along the X chromosome.
Morra
Rosa
R
Department of Biology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
Smith
Edwin R
ER
Yokoyama
Ruth
R
Lucchesi
John C
JC
D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D004265:DNA Helicases / Q000502:physiology*; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D051548:Histone Acetyltransferases; D008297:Male; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014960:X Chromosome
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D014157:Transcription Factors; C070837:mle protein, Drosophila; C082132:msl-1 protein, Drosophila; D051548:Histone Acetyltransferases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases