Polymer modelling unveils the roles of heterochromatin and nucleolar organizing regions in shaping 3D genome organization in Arabidopsis thaliana

Marco Di Stefano, Hans Wilhelm Nützmann, Marc A. Marti-Renom, Daniel Jost

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27 Citations (SciVal)


The 3D genome is characterized by a complex organization made of genomic and epigenomic layers with profound implications on gene regulation and cell function. However, the understanding of the fundamental mechanisms driving the crosstalk between nuclear architecture and (epi)genomic information is still lacking. The plant Arabidopsis thaliana is a powerful model organism to address these questions owing to its compact genome for which we have a rich collection of microscopy, chromosome conformation capture (Hi-C) and ChIP-seq experiments. Using polymer modelling, we investigate the roles of nucleolus formation and epigenomics-driven interactions in shaping the 3D genome of A. thaliana. By validation of several predictions with published data, we demonstrate that self-attracting nucleolar organizing regions and repulsive constitutive heterochromatin are major mechanisms to regulate the organization of chromosomes. Simulations also suggest that interphase chromosomes maintain a partial structural memory of the V-shapes, typical of (sub)metacentric chromosomes in anaphase. Additionally, self-attraction between facultative heterochromatin regions facilitates the formation of Polycomb bodies hosting H3K27me3-enriched gene-clusters. Since nucleolus and heterochromatin are highly-conserved in eukaryotic cells, our findings pave the way for a comprehensive characterization of the generic principles that are likely to shape and regulate the 3D genome in many species.

Original languageEnglish
Pages (from-to)1840-1858
Number of pages19
JournalNucleic Acids Research
Issue number4
Early online date14 Jan 2021
Publication statusPublished - 26 Feb 2021

Bibliographical note

Funding Information:
European Union's H2020 Framework Programme through the ERC [609989 to M.A.M.-R.]; Spanish Ministry of Science and Innovation [BFU2017-85926-P to M.A.M.-R.]; Spanish Ministry of Science and Innovation to the EMBL [to C.R.G.]; Centro de Excelencia Severo Ochoa 2013–2017 [SEV-2012-0208]; CERCA Programme/Generalitat de Catalunya, Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III; Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement; Spanish Ministry of Science and Innovation with funds from the European Regional Development Fund (ERDF) corresponding to the 2014–2020 Smart Growth Operating Program; Agence Nationale de la Recherche [ANR-18-CE12-0006-03, ANR-18-CE45-0022-01 to D.J.]; Royal Society [University Research Fellowship UF160138 to H.W.N.]; STSM Grant from COST Action CA17139. Funding for open access charge: COST Action INC (CA18127), supported by COST (European Cooperation in Science and Technology).

The Hi-C datasets analysed during the current study are available in the Sequence Read Archive (SRA) repository with accession numbers SRR1029605 from (44), SRR2626429, SRR2626163 from (45). Epigenomic data were extracted from the Supplementary Table 4 of (44). All scripts for simulations and data analysis used for this study are available on Github at https://github.com/MarcoDiS/Athaliana_simulations/

ASJC Scopus subject areas

  • Genetics


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