Abstract

Epigenetic regulation at the chromosomal level compensates for the difference in the dosage of X-linked genes between the sexes (dosage compensation). In Drosophila, this regulatory mechanism operates through the MSL complex that enhances the transcription of many genes on the X chromosome in males. The results of an investigation of the structural effects of various subunits of the complex confirmed that enriched, specific acetylation of histone H4 at lysine 16 by the histone acetyl transferase subunit MOF induced a more disorganized state of reconstituted single chromatin fibers. In addition, targeting of the MSL complex to plasmids by inclusion of the MSL assembly locus reduced the level of negative supercoiling. Similar targeting of incomplete complexes distinguished the roles that the various subunits of the complex play in this topological modification. Finally, the potential contribution of ISWI containing remodeling complexes to the architecture of compensated chromatin was analyzed and the results indicate a probable role for this remodeling factor in dosage compensation.

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