Coordinated Regulation of Heterochromatic Genes inDrosophila melanogasterMales

Abstract

Dosage compensation modifies the chromatin of X-linked genes to assure equivalent expression in sexes with unequal X chromosome dosage. In Drosophila dosage compensation is achieved by increasing expression from the male X chromosome. The ribonucleoprotein dosage compensation complex (DCC) binds hundreds of sites along the X chromosome and modifies chromatin to facilitate transcription. Loss of roX RNA, an essential component of the DCC, reduces expression from X-linked genes. Surprisingly, loss of roX RNA also reduces expression from genes situated in proximal heterochromatin and on the small, heterochromatic fourth chromosome. Mutation of some, but not all, of the genes encoding DCC proteins produces a similar effect. Reduction of roX function suppresses position effect variegation (PEV), revealing functional alteration in heterochromatin. The effects of roX mutations on heterochromatic gene expression and PEV are limited to males. A sex-limited role for the roX RNAs in autosomal gene expression was unexpected. We propose that this reflects a difference in the heterochromatin of males and females, which serves to accommodate the heterochromatic Y chromosome present in the male nucleus. roX transcripts may thus participate in two distinct regulatory systems that have evolved in response to highly differentiated sex chromosomes: compensation of X-linked gene dosage and modulation of heterochromatin.

The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes

“…In principle, differences in the chromatin structure between males and females could result from various sources: The hemizygous X chromosome is dosage compensated in males, which is accomplished by changes in the chromatin structure (Straub and Becker 2007;Gelbart and Kuroda 2009); males contain a large heterochromatic Y chromosome that could alter the stoichiometric balance of heterochromatin/euchromatin between the sexes (Weiler and Wakimoto 1995;Deng et al 2009;Lemos et al 2010;; and many genes show sex-biased expression that could be associated with sex-specific chromatin modifications. Figure 3 shows a genome-wide karyotype view of the chromatin domains derived from female and male D. miranda larvae.…”

The MSL complex: X chromosome and beyond

“…A prominent example is the global analysis of MOF, which revealed distinct binding behavior on the male X chromosome versus autosomal genes [20 ] (Figure 2). Furthermore, roX RNAs affect the regulation of genes on the fourth chromosome [47 ]. These studies raise the possibility of additional functions for these proteins/RNAs beyond dosage compensation.…”

The roles ofcis- andtrans-regulation in the evolution of regulatory incompatibilities and sexually dimorphic gene expression

“…One possible explanation for these observations is that global gene expression in Drosophila males is simply more sensitive than expression in females to genetic variation and divergence. For example, genetic perturbations affecting heterochromatin have more severe effects on genome-wide expression in males than females (Liu et al 2005;Deng et al 2009), which may reflect interactions with male-specific factors that affect both euchromatic and heterochromatic gene regulation, such as the Y chromosome (Lemos et al 2008b), or the somatic dosage compensation complex (Deng et al 2009). However, we caution that greater statistical power associated with the microarray experiments in males, e.g., due to greater technical variation or sensitivity to random environmental effects in females, could potentially contribute to the excess of divergently regulated genes detected in males.…”