title: High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila.
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.
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Fidel
authors.initials: F
authors.lastname: Ramírez
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lingg
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Toscano
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Kin Chung
authors.initials: KC
authors.lastname: Lam
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Plamen
authors.initials: P
authors.lastname: Georgiev
authors.affiliation: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors.forename: Ho-Ryun
authors.initials: HR
authors.lastname: Chung
authors.affiliation: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Lajoie
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.affiliation: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.affiliation: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-0103, USA; Howard Hughes Medical Institute.
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany. Electronic address: akhtar@ie-freiburg.mpg.de.
authors.forename: Asifa
authors.initials: A
authors.lastname: Akhtar
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C092595:Pabp2 protein, Drosophila; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C454144:roX1 protein, Drosophila