SU(VAR)3-7 Links Heterochromatin and Dosage Compensation in Drosophila

Abstract

In Drosophila, dosage compensation augments X chromosome-linked transcription in males relative to females. This process is achieved by the Dosage Compensation Complex (DCC), which associates specifically with the male X chromosome. We previously found that the morphology of this chromosome is sensitive to the amounts of the heterochromatin-associated protein SU(VAR)3-7. In this study, we examine the impact of change in levels of SU(VAR)3-7 on dosage compensation. We first demonstrate that the DCC makes the X chromosome a preferential target for heterochromatic markers. In addition, reduced or increased amounts of SU(VAR)3-7 result in redistribution of the DCC proteins MSL1 and MSL2, and of Histone 4 acetylation of lysine 16, indicating that a wild-type dose of SU(VAR)3-7 is required for X-restricted DCC targeting. SU(VAR)3-7 is also involved in the dosage compensated expression of the X-linked white gene. Finally, we show that absence of maternally provided SU(VAR)3-7 renders dosage compensation toxic in males, and that global amounts of heterochromatin affect viability of ectopic MSL2-expressing females. Taken together, these results bring to light a link between heterochromatin and dosage compensation.

Imprinting of the Y Chromosome Influences Dosage Compensation inroX1 roX2 Drosophila melanogaster

“…However, many XO males retained strong chromocenter staining, eliminating the possibility that chromocenter staining is due to recruitment of MSL proteins to the Y chromosome (Figure 2, C and D). Preferential disruption of the male polytene X chromosome has been observed for mutations in HP1, Su(var)3-7, ISWI and a super coiling protein, among others (Corona et al 2002;Spierer et al , 2008Furuhashi et al 2006). In mutant males the polytenized X typically appears short, partially decondensed and disruption of banding is readily apparent.…”

“…In the case of ISWI and super coiling factor, disruption depends on a functional dosage compensation system. Intriguingly, normal levels of Su(var)3-7 are also necessary for establishment of dosage compensation (Spierer et al 2008). To determine whether Y chromosome inheritance influences disruption of the male X chromosome in Su(var)3-7 mutants, we examined the morphology of polytene chromosomes from Su(var)3-7 males with normal or reversed sex chromosome inheritance.…”

Genetic Testing of the Hypothesis That Hybrid Male Lethality Results From a Failure in Dosage Compensation

“…Several genes encoding heterochromatin proteins such as HP1 and SU(VAR)3-7 are required in both sexes, but also show preferential effects in males on viability and X chromosome structure (Liu et al 2005;Spierer et al 2005). Su(var)3-7 shows particularly intriguing interactions, with both reduced and increased dosage leading to defects in DCC localization (Spierer et al 2008). Increased dosage of Su(var)3-7 also induces changes in X chromosome morphology and enrichment of SU(VAR)3-7, HP1, and the post-translational histone modification H3K9me2 on the X chromosome.…”

A male‐specific effect of dominant‐negative Fos

“…This demonstrates an effect on female gene expression. Third, mutations shown to affect chromosome structure can impact dosage compensation (Delattre et al, 2004;Spierer et al, 2008), similar to the Fos bZip effect proposed here.…”