X-chromosome targeting and dosage compensation are mediated by distinct domains in MSL-3.
In Drosophila, dosage compensation of X-linked genes is achieved by transcriptional upregulation of the male X chromosome. Genetic and biochemical studies have demonstrated that male-specific lethal (MSL) proteins together with roX RNAs regulate this process. Here, we show that MSL-3 is essential for cell viability and that three domains in the protein have distinct roles in dosage compensation. The chromo-barrel domain (CBD) is not necessary for MSL targeting to the male X chromosome but is important for male viability and equalization of X-linked gene transcription. The polar region cooperates with the CBD in MSL-3 function, whereas the MRG domain is responsible for targeting the protein to the X chromosome. Our results demonstrate that MSL-3 localization to the male X chromosome and transcriptional upregulation of X-linked genes are two separable functions of the MSL-3 protein.
Gene Expression Programme, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Alessia
A
Buscaino
Gaëlle
G
Legube
Asifa
A
Akhtar
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D004303:Dosage Compensation, Genetic / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D008297:Male; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C093904:msl-3 protein, Drosophila