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Nat Commun. 2019 Nov 25;10(1):5355. doi: 10.1038/s41467-019-13350-8.

Global chromatin conformation differences in the Drosophila dosage compensated chromosome X.

Author information

1
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
2
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
3
University of Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, Grenoble, France.
4
Laboratory of Biology and Modelling of the Cell, University of Lyon, ENS de Lyon, University of Claude Bernard, CNRS UMR 5239, Inserm U1210, F-69007, Lyon, France.
5
IGH, Institute of Human Genetics, CNRS UPR1142, 141 rue de la Cardonille, 34090, Montpellier, France.
6
Institute of Genetics and Molecular and Cellular Biology (IGBMC), 1 Rue Laurent Fries, 67404, Illkirch, France.
7
University of Lyon, ENS de Lyon, University of Claude Bernard, CNRS, Laboratoire de Physique, 46 allée d'Italie, 69007, Lyon, France.
8
Laboratory of Translational Immunology, Humanitas Clinical and Research Center, Via A. Manzoni 56, 20089, Rozzano, Milan, Italy.
9
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy. francesco.ferrari@ifom.eu.
10
Institute of Molecular Genetics, National Research Council, Via Abbiategrasso 207, 27100, Pavia, Italy. francesco.ferrari@ifom.eu.

Abstract

In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes. Previous literature hypothesised that a global change in chromosome structure may accompany this process. However, recent studies based on Hi-C failed to detect these differences. Here we show that global conformational differences are specifically present in the male chromosome X and detectable using Hi-C data on sex-sorted embryos, as well as male and female cell lines, by leveraging custom data analysis solutions. We find the male chromosome X has more mid-/long-range interactions. We also identify differences at structural domain boundaries containing BEAF-32 in conjunction with CP190 or Chromator. Weakening of these domain boundaries in male chromosome X co-localizes with the binding of the dosage compensation complex and its co-factor CLAMP, reported to enhance chromatin accessibility. Together, our data strongly indicate that chromosome X dosage compensation affects global chromosome structure.

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