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Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells.


ABSTRACT: 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.

SUBMITTER: Valsecchi CIK 

PROVIDER: S-EPMC6128902 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells.

Valsecchi Claudia Isabelle Keller CIK   Basilicata M Felicia MF   Semplicio Giuseppe G   Georgiev Plamen P   Gutierrez Noel Marie NM   Akhtar Asifa A  

Nature communications 20180907 1


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 mal  ...[more]

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