Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila.

Abstract

Dosage compensation in Drosophila occurs by an increase in transcription of genes on the X chromosome in males. This elevated expression requires the function of at least four loci, known collectively as the male-specific lethal (ms/) genes. The proteins encoded by two of these genes, maleless (m/e) and male-specific lethal-1 (ms/-/), are found associated with the X chromosome in males, suggesting that they act as positive regulators of dosage compensation. A specific acetylated isoform of histone H4, H4Acl6, is also detected predominantly on the male X chromosome. We have found that MLE and MSL-1 bind to the X chromosome in an identical pattern and that the pattern of H4Acl6 on the X is largely coincident with that of MLE/MSL-1. We fail to detect H4AcI6 on the X chromosome in homozygous msl males, correlating with the lack of dosage compensation in these mutants. Conversely, in Sxl mutants, we detect H4Acl6 on the female X chromosomes, coincident with an inappropriate increase in X chromosome transcription. These data suggest that synthesis or localization of H4Acl6 is controlled by the dosage compensation regulatory hierarchy. Dosage compensation may involve H4Acl6 function, potentially through interaction with the products of the msl genes.

roXRNAs Are Required for Increased Expression of X-Linked Genes inDrosophila melanogasterMales

“…The most dramatic manifestation of this is accumulation of H4Ac16, a modification linked to increased transcription, only on the male X chromosome (Turner et al 1992;Bone et al 1994). In an alternative model for the process of dosage compensation, the MSL complex sequesters MOF, thus preventing its uniform distribution.…”

Males absent on the first (MOF): from flies to humans

“…Drosophila MOF mediated acetylation of H4 at lysine 16 (H4K16) correlates with a twofold transcriptional upregulation of male X-chromosomal genes during dosage compensation and is required to balance gene expression between the sexes (Bone et al, 1994;Hilfiker et al, 1997). Both in vitro and in vivo assays have shown that H4K16Ac mediated by MOF leads to increased transcription (Akhtar and Becker, 2000;Smith et al, 2000).…”

Chromatin remodeling and transcriptional activation: the cast (in order of appearance)

“…While its elementary particle, the nucleosome (Kornberg and Thomas, 1974), is ubiquitous (Noll, 1974), chromatin over a given DNA locus can assume a great variety of markedly distinct structural states in vivo (Hebbes et al, 1994(Hebbes et al, , 1988Tumbar et al, 1999;Wu, 1980;Zaret and Yamamoto, 1984): after all, many di erent buildings can be created using the same bricks. There is very strong correlative evidence connecting chromatin structure of a speci®c locus and the level of its transcriptional activity (for example, in addition to the studies just cited, Bone et al, 1994;Braunstein et al, 1993;Jeppesen and Turner, 1993;Kuo et al, 1998). In comforting parallel, for certain loci in some model systems there is equally strong biochemical and genetic evidence that implicate speci®c protein complexes both in e ecting chemical or structural transitions in chromatin and regulating transcription over target genes (for example, Goldmark et al, 2000;Gregory et al, 1999;Moreira and Holmberg, 1999;Rundlett et al, 1998;Zhang et al, 1998).…”