TARGETING OF MOF, A PUTATIVE HISTONE ACETYL TRANSFERASE, TO THE X-CHROMOSOME OF DROSOPHILA-MELANOGASTER

Dosage compensation ensures that males with a single X chromosome have the some amount of most X-linked gene products as females with two X chromosomes. In Drosophila, this equalization is achieved by a twofold enhancement of the level of transcription of the X in males relative to each X chromosome in females. The products of al least five genes, maleless (mle), male-specific lethal 1, 2, and 3 (msl-1, msl-2, msl-3) and males absent on the first (mof), ore necessary for dosage compens ation. The proteins produced by these genes form a complex that is pre ferentially associated with numerous sites on the X chromosome in soma tic cells of males but not of females. Binding of the dosage compensat ion complex to the X chromosome is correlated with a significant incre ase in the presence of a specific histone isoform, histone 4 acetylate d at lysine 16, on this chromosome. Experimental results and sequence analysis suggest that the mof gene encodes an acetyl transferase that plays a direct role in the specific histone acetylation associated wit h dosage compensation. Recently RNA transcripts encoded by at least tw o different genes have also been found associated with the X chromosom e in males. We have studied the role played by the various components of the complex in the targeting of MOF to the X chromosome. To this en d, we have used indirect cytoimmunofluorescence to monitor the binding of these components in males carrying complete or partial loss-of-fun ction mutations as well as in XX individuals in which formation of the dosage compensation complex has been induced by genetic means. (C) 19 98 Wiley-Liss, Inc.