The nonspecific lethal complex is a transcriptional regulator in Drosophila.
Here, we report the biochemical characterization of the nonspecific lethal (NSL) complex (NSL1, NSL2, NSL3, MCRS2, MBD-R2, and WDS) that associates with the histone acetyltransferase MOF in both Drosophila and mammals. Chromatin immunoprecipitation-Seq analysis revealed association of NSL1 and MCRS2 with the promoter regions of more than 4000 target genes, 70% of these being actively transcribed. This binding is functional, as depletion of MCRS2, MBD-R2, and NSL3 severely affects gene expression genome wide. The NSL complex members bind to their target promoters independently of MOF. However, depletion of MCRS2 affects MOF recruitment to promoters. NSL complex stability is interdependent and relies mainly on the presence of NSL1 and MCRS2. Tethering of NSL3 to a heterologous promoter leads to robust transcription activation and is sensitive to the levels of NSL1, MCRS2, and MOF. Taken together, we conclude that the NSL complex acts as a major transcriptional regulator in Drosophila.
Raja
Sunil Jayaramaiah
SJ
Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Charapitsa
Iryna
I
Conrad
Thomas
T
Vaquerizas
Juan M
JM
Gebhardt
Philipp
P
Holz
Herbert
H
Kadlec
Jan
J
Fraterman
Sven
S
Luscombe
Nicholas M
NM
Akhtar
Asifa
A
D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D049750:Genome, Insect; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D051548:Histone Acetyltransferases; C111063:mof protein, Drosophila