Global chromatin conformation differences in the Drosophila dosage compensated chromosome X

Koustav Pal, Mattia Forcato, Daniel Jost, Thomas Sexton, Cédric Vaillant, Elisa Salviato, Emilia Maria Cristina Mazza, Enrico Lugli, Giacomo Cavalli and Francesco Ferrari ()
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Koustav Pal: IFOM, the FIRC Institute of Molecular Oncology
Mattia Forcato: University of Modena and Reggio Emilia
Daniel Jost: University of Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG
Thomas Sexton: IGH, Institute of Human Genetics, CNRS UPR1142
Cédric Vaillant: University of Lyon, ENS de Lyon, University of Claude Bernard, CNRS, Laboratoire de Physique
Elisa Salviato: IFOM, the FIRC Institute of Molecular Oncology
Emilia Maria Cristina Mazza: Humanitas Clinical and Research Center
Enrico Lugli: Humanitas Clinical and Research Center
Giacomo Cavalli: IGH, Institute of Human Genetics, CNRS UPR1142
Francesco Ferrari: IFOM, the FIRC Institute of Molecular Oncology

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13350-8

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