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First published online January 23, 2009
doi: 10.1242/10.1242/dev.027656
1 Centre de Regulació Genòmica (CRG-UPF), Gene Regulation
Programme, Dr Aiguader 88, 08003 Barcelona, Spain.
2 Departamento de Genética, Facultad Ciencias Biológicas,
Universitad de Valencia, Dr Moliner 50, 46100 Burjasot, Spain.
* Author for correspondence (e-mail: fatima.gebauer{at}crg.es)
Accepted 15 December 2008
Dosage compensation in Drosophila melanogaster involves the assembly of the MSL-2-containing dosage compensation complex (DCC) on the single X chromosome of male flies. Translational repression of msl-2 mRNA blocks this process in females. Previous work indicated that the ubiquitous protein Upstream of N-ras (UNR) is a necessary co-factor for msl-2 repression in vitro. Here, we explore the function of UNR in vivo. Hypomorphic Unr mutant flies showed DCC assembly on high-affinity sites in the female X chromosomes, confirming that UNR inhibits dosage compensation in female flies. Unexpectedly, male mutant flies and UNR-depleted SL2 cells showed decreased DCC binding to the X chromosome, suggesting a role for UNR in DCC assembly or targeting. Consistent with this possibility, UNR overexpression resulted in moderate loss of DCC from the male X chromosome and predominant male lethality. Immunoprecipitation experiments revealed that UNR binds to roX1 and roX2, the non-coding RNA components of the DCC, providing possible targets for UNR function in males. These results uncover dual sex-specific functions of UNR in dosage compensation: to repress DCC formation in female flies and to promote DCC assembly on the male X chromosome.
Key words: UNR, Dosage compensation, DCC, MSL, Translation, roX1/2
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