The NSL complex regulates housekeeping genes in Drosophila.
MOF is the major histone H4 lysine 16-specific (H4K16) acetyltransferase in mammals and Drosophila. In flies, it is involved in the regulation of X-chromosomal and autosomal genes as part of the MSL and the NSL complexes, respectively. While the function of the MSL complex as a dosage compensation regulator is fairly well understood, the role of the NSL complex in gene regulation is still poorly characterized. Here we report a comprehensive ChIP-seq analysis of four NSL complex members (NSL1, NSL3, MBD-R2, and MCRS2) throughout the Drosophila melanogaster genome. Strikingly, the majority (85.5%) of NSL-bound genes are constitutively expressed across different cell types. We find that an increased abundance of the histone modifications H4K16ac, H3K4me2, H3K4me3, and H3K9ac in gene promoter regions is characteristic of NSL-targeted genes. Furthermore, we show that these genes have a well-defined nucleosome free region and broad transcription initiation patterns. Finally, by performing ChIP-seq analyses of RNA polymerase II (Pol II) in NSL1- and NSL3-depleted cells, we demonstrate that both NSL proteins are required for efficient recruitment of Pol II to NSL target gene promoters. The observed Pol II reduction coincides with compromised binding of TBP and TFIIB to target promoters, indicating that the NSL complex is required for optimal recruitment of the pre-initiation complex on target genes. Moreover, genes that undergo the most dramatic loss of Pol II upon NSL knockdowns tend to be enriched in DNA Replication-related Element (DRE). Taken together, our findings show that the MOF-containing NSL complex acts as a major regulator of housekeeping genes in flies by modulating initiation of Pol II transcription.
Max-Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
Kin Chung
KC
Lam
Friederike
F
Mühlpfordt
Juan M
JM
Vaquerizas
Sunil Jayaramaiah
SJ
Raja
Herbert
H
Holz
Nicholas M
NM
Luscombe
Thomas
T
Manke
Asifa
A
Akhtar
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D049750:Genome, Insect; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins
C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; C553663:NSL1 protein, Drosophila; D009687:Nuclear Proteins; C553193:Rcd5 protein, Drosophila; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II