HP1 drives de novo 3D genome reorganization in early Drosophila embryos

Fides Zenk, Yinxiu Zhan, Pavel Kos, Eva Löser, Nazerke Atinbayeva, Melanie Schächtle, Guido Tiana, Luca Giorgetti () and Nicola Iovino ()
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Fides Zenk: Max Planck Institute of Immunobiology and Epigenetics
Yinxiu Zhan: Friedrich Miescher Institute for Biomedical Research
Pavel Kos: Friedrich Miescher Institute for Biomedical Research
Eva Löser: Max Planck Institute of Immunobiology and Epigenetics
Nazerke Atinbayeva: Max Planck Institute of Immunobiology and Epigenetics
Melanie Schächtle: Max Planck Institute of Immunobiology and Epigenetics
Guido Tiana: Università degli Studi di Milano and INFN
Luca Giorgetti: Friedrich Miescher Institute for Biomedical Research
Nicola Iovino: Max Planck Institute of Immunobiology and Epigenetics

Nature, 2021, vol. 593, issue 7858, 289-293

Abstract: Abstract Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. The binding of HP1a at pericentromeric heterochromatin is required to establish clustering of pericentromeric regions. Moreover, HP1a binding within chromosome arms is responsible for overall chromosome folding and has an important role in the formation of B-compartment regions. However, depletion of HP1a does not affect the A-compartment, which suggests that a different molecular mechanism segregates active chromosome regions. Our work identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early embryo.

Date: 2021
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DOI: 10.1038/s41586-021-03460-z

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