The MLE Subunit of the Drosophila MSL Complex Uses Its ATPase Activity for Dosage Compensation and Its Helicase Activity for Targeting

Abstract

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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

We are grateful to Eugene Koonin for his help in identifying putative mutations in domain III and to Mitzi Kuroda for fly stocks. We thank Arri Eisen for his comments on the manuscript. We acknowledge the highly skilled technical help of Huiping Ling.

This research was supported by grant GM15691 from the National Institutes of Health.