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Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells
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Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells
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Journal Article
Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells
2018
Overview
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.
In
Drosophila
the Male-Specific Lethal complex (MSLc) mediates upregulation of the single male X chromosome. Here the authors provide evidence that MSL2 also targets autosomal genes required for proper development and that MSL2 binds and similarly regulates mouse orthologues.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38
/ 38/15
/ 38/39
/ 38/89
/ 38/91
/ 45/100
/ 631/136
/ 64/24
/ 64/60
/ Animals
/ Chromatin Assembly and Disassembly
/ Compound Eye, Arthropod - growth & development
/ DNA-Binding Proteins - physiology
/ Dosage
/ Dosage Compensation, Genetic
/ Drosophila Proteins - physiology
/ Embryonic Stem Cells - metabolism
/ Female
/ Gene Expression Regulation, Developmental
/ Genes
/ Humanities and Social Sciences
/ Insects
/ Lysine
/ Male
/ Mice
/ Nuclear Proteins - physiology
/ Proteins
/ Science
/ Transcription Factors - physiology
