Chromodomains are protein–RNA interaction modules

Abstract

In Drosophila, compensation for the reduced dosage of genes located on the single male X chromosome involves doubling their expression in relation to their counterparts on female X chromosomes1. Dosage compensation is an epigenetic process involving the specific acetylation of histone H4 at lysine 16 by the histone acetyltransferase MOF2,3,4,5. Although MOF is expressed in both sexes, it only associates with the X chromosome in males. Its absence causes male-specific lethality6. MOF is part of a chromosome-associated complex comprising male-specific lethal (MSL) proteins and at least one non-coding roX RNA7. How MOF is integrated into the dosage compensation complex is unknown. Here we show that association of MOF with the male X chromosome depends on its interaction with RNA. MOF specifically binds through its chromodomain to roX2 RNA in vivo. In vitro analyses of the MOF and MSL-3 chromodomains indicate that these chromodomains may function as RNA interaction modules. Their interaction with non-coding RNA may target regulators to specific chromosomal sites.

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Figure 1: Localization of MOF to the X chromosome is RNase-sensitive.
Figure 2: MOF binds roX2 RNA in vivo.
Figure 3: MOF interacts with RNA in vitro and in vivo through the chromodomain.
Figure 4: Chromodomain in MSL-3 is also sufficient for interaction with RNA in vitro.

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Acknowledgements

A.A. acknowledges support from the Human Frontier Science Program. We thank M. Kuroda for providing antibodies; T. Straub for GST control protein; D. Ostareck and G. Mengus for protocols; I. Vetter and C. Schwarzlose for technical assistance; and N. Sadoni for help with arranging images. We are also grateful to W. Hörz, S. Kass and members of the laboratory for critical reading of the manuscript and helpful discussion.

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Correspondence to Peter B. Becker.

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Akhtar, A., Zink, D. & Becker, P. Chromodomains are protein–RNA interaction modules. Nature 407, 405–409 (2000). https://doi.org/10.1038/35030169

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