Work

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

Year: 2018

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-018-05642-2

Authors: Claudia Isabelle Keller Valsecchi, M. Felicia Basilicata, Giuseppe Semplicio, Plamen Georgiev, Noel Marie Gutierrez, Asifa Akhtar

Institution: Max Planck Institute of Immunobiology and Epigenetics

Language: English

Topic: Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funder: Deutsche Forschungsgemeinschaft