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

TY - JOUR

T1 - High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila

AU - Ramírez, Fidel

AU - Lingg, Thomas

AU - Toscano, Sarah

AU - Lam, Kin Chung

AU - Georgiev, Plamen

AU - Chung, Ho-Ryun

AU - Lajoie, Bryan R

AU - de Wit, Elzo

AU - Zhan, Ye

AU - de Laat, Wouter

AU - Dekker, Job

AU - Manke, Thomas

AU - Akhtar, Asifa

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.molcel.2015.08.024

DO - 10.1016/j.molcel.2015.08.024

M3 - Article

C2 - 26431028

SN - 1097-2765

VL - 60

SP - 146

EP - 162

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -