Background: Gene dosage change is a mild perturbation that is a valuable tool for pathway reconstruction in Drosophila. While it is often assumed that reducing gene dose by half leads to two-fold less expression, there is partial autosomal dosage compensation in Drosophila, which may be mediated by feedback or buffering in expression networks.Results: We profiled expression in engineered flies where gene dose was reduced from two to one. While expression of most one-dose genes was reduced, the gene-specific dose responses were heterogeneous. Expression of two-dose genes that are first-degree neighbors of one-dose genes in novel network models also changed expression, and the directionality of change depended on the response of one-dose genes.Conclusions: Our data indicate that expression perturbation propagates in network space. Autosomal compensation, or the lack thereof, is a gene-specific response, largely mediated by interactions with the rest of the transcriptome.
|Original language||English (US)|
|State||Published - Apr 24 2012|
Bibliographical noteFunding Information:
We thank the Drosophila Stock Center (Bloomington, IN, USA) and Steve Russell (Cambridge, UK) for flies and the Spyros Artavanis-Tsakonas lab (Boston, MA, USA) for sharing pre-publication protein-protein interaction data. We thank fellow members of our labs for stimulating discussion, advice, feedback, and encouragement. This research was supported by the Intramural Research Programs of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Library of Medicine (NLM), and National Institute of Standards and Technology (NIST). Certain commercial equipment, instruments, or materials are identified in this document. Such identification does not imply recommendation or endorsement by NIH or NIST, nor does it imply that the products identified are necessarily the best available for the purpose.