Dual sex-specific functions of Drosophila Upstream of N-ras in the control of X chromosome dosage compensation.
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.
Patalano
Solenn
S
Centre de Regulació Genòmica, 08003 Barcelona, Spain.
Mihailovich
Marija
M
Belacortu
Yaiza
Y
Paricio
Nuria
N
Gebauer
Fátima
F
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004251:DNA Transposable Elements / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000172:deficiency / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics*; D005260:Female; D005298:Fertility; D008297:Male; D011485:Protein Binding; D022661:RNA, Untranslated / Q000378:metabolism; D012727:Sex Characteristics; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*
D002843:Chromatin; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D022661:RNA, Untranslated; C509278:UNR protein, Drosophila; C539613:MSL2 protein, mouse; D044767:Ubiquitin-Protein Ligases