High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Biochemistry, Biophysics, and Structural Biology | Genetics and Genomics | Systems Biology
Dosage compensation mechanisms provide a paradigm to study the contribution of chromosomal conformation toward targeting and spreading of epigenetic regulators over a specific chromosome. By using Hi-C and 4C analyses, we show that high-affinity sites (HAS), landing platforms of the male-specific lethal (MSL) complex, are enriched around topologically associating domain (TAD) boundaries on the X chromosome and harbor more long-range contacts in a sex-independent manner. Ectopically expressed roX1 and roX2 RNAs target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. We show that the MSL complex regulates nucleosome positioning at HAS, therefore acting locally rather than influencing the overall chromosomal architecture. We propose that the sex-independent, three-dimensional conformation of the X chromosome poises it for exploitation by the MSL complex, thereby facilitating spreading in males.
DOI of Published Version
Mol Cell. 2015 Oct 1;60(1):146-62. doi: 10.1016/j.molcel.2015.08.024. Link to article on publisher's site
Ramirez, Fidel; Lingg, Thomas; Toscano, Sarah; Lam, Kin Chung.; Georgiev, Plamen; Chung, Ho-Ryun; Lajoie, Bryan R.; de Wit, Elzo; Zhan, Ye; de Laat, Wouter; Dekker, Job; Manke, Thomas; and Akhtar, Asifa, "High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila" (2015). Program in Systems Biology Publications and Presentations. 75.