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


Tikhonova Evgeniya1,Mariasina Sofia2,Efimov Sergey3,Polshakov Vladimir2ORCID,Maksimenko Oksana4ORCID,Georgiev Pavel1ORCID,Bonchuk Artem14ORCID


1. Department of the Control of Genetic Processes, Institute of Gene Biology , Moscow  119334, Russia

2. Center for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University , Moscow  119991, Russia

3. NMR Laboratory, Institute of Physics, Kazan Federal University , Kazan  420008, Russia

4. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology , Moscow  119334, Russia


Abstract Transcriptional regulators select their targets from a large pool of similar genomic sites. The binding of the Drosophila dosage compensation complex (DCC) exclusively to the male X chromosome provides insight into binding site selectivity rules. Previous studies showed that the male-specific organizer of the complex, MSL2, and ubiquitous DNA-binding protein CLAMP directly interact and play an important role in the specificity of X chromosome binding. Here, we studied the highly specific interaction between the intrinsically disordered region of MSL2 and the N-terminal zinc-finger C2H2-type (C2H2) domain of CLAMP. We obtained the NMR structure of the CLAMP N-terminal C2H2 zinc finger, which has a classic C2H2 zinc-finger fold with a rather unusual distribution of residues typically used in DNA recognition. Substitutions of residues in this C2H2 domain had the same effect on the viability of males and females, suggesting that it plays a general role in CLAMP activity. The N-terminal C2H2 domain of CLAMP is highly conserved in insects. However, the MSL2 region involved in the interaction is conserved only within the Drosophila genus, suggesting that this interaction emerged during the evolution of a mechanism for the specific recruitment of the DCC on the male X chromosome in Drosophilidae.


Russian Foundation for Basic Research

Russian Science Foundation

Ministry of Science and Higher Education of the Russian Federation

Interdisciplinary Scientific and Educational School of Moscow University


Oxford University Press (OUP)



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