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Valsecchi, C.I.K., Basilicata, M.F., Semplicio, G., Georgiev, P., Gutierrez, N.M., Akhtar, A. (2018). Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells.  Nat. Commun. 9(1): 3626.
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Research paper

Haploinsufficiency and aneuploidy are two phenomena, where gene dosage alterations cause severe defects ultimately resulting in developmental failures and disease. One remarkable exception is the X chromosome, where copy number differences between sexes are buffered by dosage compensation systems. In Drosophila, the Male-Specific Lethal complex (MSLc) mediates upregulation of the single male X chromosome. The evolutionary origin and conservation of this process orchestrated by MSL2, the only male-specific protein within the fly MSLc, have remained unclear. Here, we report that MSL2, in addition to regulating the X chromosome, targets autosomal genes involved in patterning and morphogenesis. Precise regulation of these genes by MSL2 is required for proper development. This set of dosage-sensitive genes maintains such regulation during evolution, as MSL2 binds and similarly regulates mouse orthologues via Histone H4 lysine 16 acetylation. We propose that this gene-by-gene dosage compensation mechanism was co-opted during evolution for chromosome-wide regulation of the Drosophila male X.

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PMC6128902 (PMC) (EuropePMC)
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    Nat. Commun.
    Nature communications
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