The Drosophila MSL Complex Acetylates Histone H4 at Lysine 16, a Chromatin Modification Linked to Dosage Compensation

Abstract

In Drosophila, dosage compensation—the equalization of most X-linked gene products in males and females—is achieved by a twofold enhancement of the level of transcription of the X chromosome in males relative to each X chromosome in females. A complex consisting of at least five gene products preferentially binds the X chromosome at numerous sites in males and results in a significant increase in the presence of a specific histone isoform, histone 4 acetylated at lysine 16. Recently, RNA transcripts (roX1 and roX2) encoded by two different genes have also been found associated with the X chromosome in males. We have partially purified a complex containing MSL1, -2, and -3, MOF, MLE, and roX2 RNA and demonstrated that it exclusively acetylates H4 at lysine 16 on nucleosomal substrates. These results demonstrate that the MSL complex is responsible for the specific chromatin modification characteristic of the X chromosome in Drosophila males.

ACKNOWLEDGMENTS

We thank Brian Turner (Birmingham, United Kingdom) for providing us with the anti-H4Ac16 sera and Michael Koelle for the pMK33/pMtHy vector. We thank Melissa Gilbert and Hisa Tajima for technical assistance and members of the Allis and Lucchesi laboratories for helpful discussions.

This work was supported by grants from the National Institutes of Health to J.C.L. (GM15961) and to C.D.A. (GM53512) and from the Human Frontiers of Science Program to C.D.A.