N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

Abstract

The male-specific lethal dosage compensation complex (MSL complex or DCC), which consists of five proteins and two non-coding roX RNAs, is necessary for the transcriptional enhancement of X-linked genes to compensate for the sex chromosome monosomy in Drosophila XY males, compared with XX females. MSL2 is a single protein component of the DCC that is expressed only in males and is essential for the specific recruitment of the DCC to the high-affinity “entry” sites (HASs) on the X chromosome. MSL2, together with MSL1, forms the heterotetrameric DCC core. Here, we demonstrated that the N-terminal unstructured region of MSL1 interacts with many different DNA-binding proteins that contain clusters of the C2H2 zinc-finger domains. Amino acid deletions in the N-terminal region of MSL1 strongly affect the binding of the DCC to the HASs on the male X chromosome. However, the binding of MSL2 to autosomal promoters was unaffected by amino acid deletions in MSL1. Males expressing mutant variants of MSL1 died during the larvae stage, demonstrating the critical role played by the N-terminal region in DCC activity. Our results suggest that MSL1 interacts with a variety of DNA-binding proteins to increase the specificity of DCC recruitment to the male X chromosome.BulletsThe N-terminal region of MSL1 interacts with 14 C2H2-type zinc-finger DNA-binding proteinsThe N-terminus of MSL1 is critical for the specific recruitment of the MSL complex to the X chromosomeThe N-terminus of MSL1 is important for the binding of MSL2 to a small fraction of autosomal promoters

Structural basis for interaction between CLAMP and MSL2 proteins involved in the specific recruitment of the dosage compensation complex in Drosophila

“…Interaction of the CLAMP N-terminal zinc-finger with MSL2 is highly specific: in Y2H screening, we revealed that MSL2 only interacted with CLAMP and not with any other protein of the tested 152 multizinc-finger Drosophila transcription factors (14). Here we examined the structural basis for the interaction between the CLAMP and MSL2 proteins using NMR techniques and mutagenic screening complemented with in vivo experiments.…”