Incorporation of the Noncoding roX RNAs Alters the Chromatin-Binding Specificity of the Drosophila MSL1/MSL2 Complex

Abstract

The male-specific lethal (MSL) protein-RNA complex is required for X chromosome dosage compensation in Drosophila melanogaster. The MSL2 and MSL1 proteins form a complex and are essential for X chromosome binding. In addition, the MSL complex must integrate at least one of the noncoding roX RNAs for normal X chromosome binding. Here we find the amino-terminal RING finger domain of MSL2 binds as a complex with MSL1 to the heterochromatic chromocenter and a few sites on the chromosome arms. This binding required the same amino-terminal basic motif of MSL1 previously shown to be essential for binding to high-affinity sites on the X chromosome. While the RING finger domain of MSL2 is sufficient to increase the expression of roX1 in females, activation of roX2 requires motifs in the carboxyl-terminal domain. Binding to hundreds of sites on the X chromosome and efficient incorporation of the roX RNAs into the MSL complex require proline-rich and basic motifs in the carboxyl-terminal domain of MSL2. We suggest that incorporation of the roX RNAs into the MSL complex alters the binding specificity of the chromatin-binding module formed by the amino-terminal domains of MSL1 and MSL2.

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Incorporation of the Noncoding roX RNAs Alters the Chromatin-Binding Specificity of the Drosophila MSL1/MSL2 Complex

SUPPLEMENTAL MATERIAL

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

ACKNOWLEDGMENTS

We are grateful to Esther Belikoff for excellent technical assistance and to Corey Laverty for comments on the manuscript. We thank Mitzi Kuroda, Rick Kelley, and John Lucchesi for generously sending plasmid DNAs, antibodies, and fly strains.

This research was funded by grant MAU204 from the Royal Society of New Zealand Marsden Fund.