The male-specific lethal (MSL) complex of Drosophila is responsible for the presence of a monoacetylated isoform of histone H4 (H4Ac16), found exclusively on the X chromosome of males. This particular covalent modification of histone H4 is correlated with a 2-fold enhancement of the transcription of most X-linked genes in Drosophila males, which is the basis of dosage compensation in this organism. Although widespread along the X chromosome, the MSL complex is not distributed uniformly, as can be seen by the indirect cytoimmunofluorescence staining of larval salivary-gland polytene chromosomes. This distribution pattern has been interpreted as a reflection of the tissue-specific transcriptional activity of the larval salivary gland and as an indication that the MSL complex associates with active chromatin. We have tested this hypothesis by comparing the chromosomal distribution of the complex in two different tissues. We performed this comparison by following the pattern of association of the complex at a specific site on salivary-gland chromosomes during larval development and determining whether an ectopic promoter located in a complexdevoid region of the X chromosome is able to attract the complex upon activation. Our results indicate that, in contrast to other chromatin-remodeling complexes that enhance transcription, the MSL complex targets active chromatin.
In eukaryotic cells, the architectural organization of chromatin is unfavorable to the process of transcription; it must be altered for the preinitiation complex to access promoter regions and for transcription to begin. The necessary alteration in the association of DNA and nucleosomes can be achieved by the covalent modification of the N-terminal tails of histones in a manner that alters their affinity for the DNA. Such modifications include acetylation, phosphorylation, methylation, ADP-ribosylation, and ubiquitination. Acetylation is the responsibility of multiprotein complexes that target histone acetyltransferases to their site of action in chromatin. A change in the association of DNA and nucleosomes also can be achieved by using the energy released by ATP hydrolysis. This type of chromatin remodeling is mediated by multiprotein complexes that contain an ATPaseenzymatic subunit (1-4).In Drosophila, the male-specific lethal (MSL) complex is responsible for enhancing the rate of transcription of most X-linked genes in males, thereby achieving an equal level of gene products in males and females. Among its protein components, this complex includes both a histone acetyltransferase [males absent on the first (MOF)] and an adenosinetriphosphatase with demonstrated helicase activity [maleless (MLE)]; the latter feature distinguishes it from all other known chromatin complexes. Furthermore, the MSL complex contains at least one of two noncoding RNAs produced by the roX1 and roX2 (RNA on the X) genes (5-7). The function of this complex is unlikely to be the initiation of gene activity. This conclusion is derived from the observation that X-linked genes ar...