High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila

Fidel Ramírez, Thomas Lingg, Sarah Toscano, Kin Chung Lam, Plamen Georgiev, Ho-Ryun Chung, Bryan R Lajoie, Elzo de Wit, Ye Zhan, Wouter de Laat, Job Dekker, Thomas Manke, Asifa Akhtar

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)146-62
Number of pages17
JournalMolecular Cell
Volume60
Issue number1
DOIs
Publication statusPublished - 01 Oct 2015

Fingerprint

Dive into the research topics of 'High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila'. Together they form a unique fingerprint.

Cite this