Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila.
The Male-Specific Lethal (MSL) complex regulates dosage compensation of the male X chromosome in Drosophila. Here, we report the crystal structure of its MSL1/MSL2 core, where two MSL2 subunits bind to a dimer formed by two molecules of MSL1. Analysis of structure-based mutants revealed that MSL2 can only interact with the MSL1 dimer, but MSL1 dimerization is MSL2 independent. We show that Msl1 is a substrate for Msl2 E3 ubiquitin ligase activity. ChIP experiments revealed that Msl1 dimerization is essential for targeting and spreading of the MSL complex on X-linked genes; however, Msl1 binding to promoters of male and female cells is independent of the dimer status and other MSL proteins. Finally, we show that loss of Msl1 dimerization leads to male-specific lethality. We propose that Msl1-mediated dimerization of the entire MSL complex is required for Msl2 binding, X chromosome recognition, and spreading along the X chromosome.
Max-Planck-Institut für Immunbiologie und Epigenetik, Stübeweg 51, 79108 Freiburg im Breisgau, Germany.
Erinc
E
Hallacli
Michael
M
Lipp
Plamen
P
Georgiev
Clare
C
Spielman
Stephen
S
Cusack
Asifa
A
Akhtar
Jan
J
Kadlec
D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D055503:Protein Multimerization; D014157:Transcription Factors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C094166:msl-2 protein, Drosophila