Abstract
The ribonucleoprotein Male Specific Lethal (MSL) complex is required for X chromosome dosage compensation in Drosophila melanogaster males. Beginning at 3 h of development the MSL complex binds transcribed X-linked genes and modifies chromatin. A subset of MSL complex proteins, including MSL1 and MSL3, is also necessary for full expression of autosomal heterochromatic genes in males, but not females. Loss of the non-coding roX RNAs, essential components of the MSL complex, lowers the expression of heterochromatic genes and suppresses position effect variegation (PEV) only in males, revealing a sex-limited disruption of heterochromatin. To explore the molecular basis of this observation we examined additional proteins that participate in compensation and found that MLE, but not Jil-1 kinase, contributes to heterochromatic gene expression. To determine if identical regions of roX RNA are required for dosage compensation and heterochromatic silencing, we tested a panel of roX1 transgenes and deletions and find that the X chromosome and heterochromatin functions are separable by some mutations. Chromatin immunoprecipitation of staged embryos revealed widespread autosomal binding of MSL3 before and after localization of the MSL complex to the X chromosome at 3 h AEL. Autosomal MSL3 binding was dependent on MSL1, supporting the idea that a subset of MSL proteins associates with chromatin throughout the genome during early development. The broad localization of these proteins early in embryogenesis supports the idea of direct action at autosomal sites. We postulate that this may contribute to the sex-specific differences in heterochromatin that we, and others, have noted.
Highlights
Heterochromatin, which comprises one third of the Drosophila melanogaster genome, makes up half of the X chromosome, most of the 4th chromosome and the entire Y chromosome
Ectopic expression of Male Specific Lethal 2 (MSL2) in females induces formation of Male Specific Lethal (MSL) complexes that localize to both X chromosomes, but expression of MSL2 has no influence on Position Effect Variegation (PEV) of reporters in autosomal heterochromatin [4, 5]
A central question raised by this study is how factors known for their role in X chromosome dosage compensation modulate autosomal heterochromatin
Summary
Heterochromatin, which comprises one third of the Drosophila melanogaster genome, makes up half of the X chromosome, most of the 4th chromosome and the entire Y chromosome. The intact MSL complex is not required for the heterochromatic function as loss of Male Specific Lethal 2 (MSL2), an essential member of MSL complex, had no effect on expression of heterochromatic genes or PEV [4, 5] These findings rule out indirect effects of dosage compensation failure, such as relocalization of X chromosome-bound factors or reduced expression of an X-linked protein essential for heterochromatin formation. Two additional MSL proteins, Male Specific Lethal 1 and 3 (MSL1, MSL3) are necessary for full expression of autosomal heterochromatic genes in males [4] Taken together, these findings indicate differences in autosomal heterochromatin in the sexes that are revealed by loss of a subset of the molecules in the MSL complex. The sensitivity of males to the loss of these factors reveals an underlying difference in autosomal heterochromatin in the sexes
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