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Drosophila Dosage Compensation Involves Enhanced Pol II Recruitment to Male X-Linked Promoters

Science  10 Aug 2012:
Vol. 337, Issue 6095, pp. 742-746
DOI: 10.1126/science.1221428

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Promoting the Male X Chromosome

In mammals and fruit flies, females have a double dose of the X chromosome compared to males, and to compensate for this imbalance, in fruit flies, transcription from across most of the male X chromosome is boosted by twofold. Conrad et al. (p. 742, published online 19 July) measured the binding of RNA polymerase II, responsible for the majority of the transcription on the X chromosome, and found a consistent increase at the promoters of genes on the male X chromosome. Thus, the increase in transcription on the male X chromosome is not driven by increased rates of transcriptional elongation, as has been suggested previously, but must involve up-regulation of transcription initiation.

Abstract

Through hyperacetylation of histone H4 lysine 16 (H4K16), the male-specific lethal (MSL) complex in Drosophila approximately doubles transcription from the single male X chromosome in order to match X-linked expression in females and expression from diploid autosomes. By obtaining accurate measurements of RNA polymerase II (Pol II) occupancies and short promoter-proximal RNA production, we detected a consistent, genome-scale increase in Pol II activity at the promoters of male X-linked genes. Moreover, we found that enhanced Pol II recruitment to male X-linked promoters is largely dependent on the MSL complex. These observations provide insights into how global modulation of chromatin structure by histone acetylation contributes to the precise control of Pol II function.

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