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4DGenome - ERC Synergy project

4DGenome - ERC Synergy project4DGenome - ERC Synergy project

  • Description
  • Objectives
  • Research Groups
  • Publications

Dynamics of genome architecture in stable and transient changes in gene expression

Chromosomes and genes are non-randomly positioned in the cell nucleus and the vision of a dynamic and complex organization of the nucleus is replacing the classical view of genomes as linear sequences. Process compartmentalization and spatial location of genes is proposed to modulate the transcriptional output of the genomes. However, how the interplay between genome structure and gene regulation is established and maintained still has to be discovered. The aim of this project is to explore whether the genome three-dimensional (3D) structure acts as an information store that modulates transcription in response to external stimuli. In an interdisciplinary team effort, we study the conformation of the genome at various scales, from the nucleosome fiber to the distribution of chromosomes territories in the nuclear space. We generate high-resolution 3D models of the spatial organization of the genomes of distinct eukaryotic cell types in interphase to identify differences in the chromatin landscape. We notably follow the time course of structural changes in response to cues that affect gene expression either transiently or permanently: changes in genome structure during transient hormonal response of differentiated cells and stable trans-differentiation of B cells to macrophages. We are also establishing novel functional strategies, based on targeted and high throughput reporter assays, to assess the relevance of the spatial environment on gene regulation. Using modeling and computational approaches, we will integrate high-resolution data from chromosome interactions, super-resolution images and “omics” datasets. Our long-term plan is to bring to the front the view that the chromosome is a dynamic 3D fiber. To this end we will implement a 3D browser to map genomic features as they really localize in the nucleus, for a better characterizing how genome architecture dynamically integrates external signals to orchestrate gene expression.

  • Describe changes in the 3D organization of the genome during stable transdifferentiation and transient hormonal response

 

  • Integrate and visualize multi-D data

 

  • Establish correlations between the 3D organization of the genome and transcription

 

  • Discover mechanisms of establishment, maintenance and modification of the 3D organization of the genome

 

    No. TOTAL PUBLICATIONS: 13
    PREPRINT
    Vidal E, Le Dily F, Quilez J, Stadhouders R, Cuartero Y, Graf T, Martí-Renom MA, Beato M, Filion GJ.
    OneD: increasing reproducibility of Hi-C Samples with abnormal karyotypes.
    OneD: increasing reproducibility of Hi-C Samples with abnormal karyotypes. bioRxiv. 9/6/2017.
    [doi:10.1101/148254]
    Quilez J, Vidal E, Le Dily F, Serra F, Cuartero Y, Stadhouders R, Filion G, Thomas Graf, Marti-Renom MA, Beato M.
    Managing the analysis of high-throughput sequencing data.
    Managing the analysis of high-throughput sequencing data. bioRxiv. 10/5/2017.
    [doi:10.1101/136358]
    Stadhouders R, Vidal E, Serra F, Di Stefano B, Le Dily F, Quilez J, Gomez A, Collombet S, Berenguer C, Cuartero Y, Hecht J, Filion G, Beato M, Marti-Renom MA, Graf T.
    Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming.
    Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming. bioRxiv. 30/4/2017.
    [doi:10.1101/132456]
    OPEN ACCESS
    Corrales M, Rosado A, Cortini R, van Arensbergen J, van Steensel B, Filion GJ.
    Clustering of Drosophila housekeeping promoters facilitates their expression.
    Clustering of Drosophila housekeeping promoters facilitates their expression. Genome Res. 2017 Jul;27(7):1153-1161. 12/04/2017.
    [doi:10.1101/gr.211433.116]
    Le Dily F, Serra F, Marti-Renom, MA.
    3D modeling of chromatin structure: is there a way to integrate and reconcile single cell and population experimental data?
    3D modeling of chromatin structure: is there a way to integrate and reconcile single cell and population experimental data? WIREs Comput Mol Sci, e1308. 10/04/2017.
    [doi:10.1002/wcms.1308]
    Krijger PHL, Di Stefano B, de Wit E, Limone F, van Oevelen C, de Laat W, Graf T.
    Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming.
    Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming. Cell Stem Cell 18 (5), 597-610. 05/05/2016.
    [doi:10.1016/j.stem.2016.01.007]
    Serra F, Baù D, Goodstadt M, Castillo D, Filion G, Marti-Renom MA.
    Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors.
    Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors. PLoS Computational Biology. 00/00/2017.
    [doi:]
    Trussart M, Yus E, Martinez S, Baù D, Tahara YO, Pengo T, Widaja M, Kretschmer S, Swoger J, Djordjevic S, Turnbull L, Whitchurch C, Miyata M, Marti-Renom MA, Lluch-Senar M, Serrano L.
    Defined chromosome structure in the genome- reduced bacterium Mycoplasma pneumoniae.
    Defined chromosome structure in the genome- reduced bacterium Mycoplasma pneumoniae. Nature Communications 8:14665. 08/03/2015.
    [doi:10.1038/ncomms14665]
    Trussart M, Serra F, Baù D, Junier I, Serrano L, Marti-Renom MA.
    Assessing the limits of restraint-based 3D modeling of genomes and genomic domains.
    Assessing the limits of restraint-based 3D modeling of genomes and genomic domains. Nucleic Acids Res 43 3465-3477. 20/04/2015. F.I.:8.808
    [doi:10.1093/nar/gkv221]
    OTHER
    le Dily F, Beato M.
    TADs as modular and dynamic units for gene regulation by hormones.
    TADs as modular and dynamic units for gene regulation by hormones. FEBS Letters 589 (2015) 2885–2892. 24/05/2015.
    [doi:10.1016/j.febslet.2015.05.026]
    Junier I, Spill YG, Marti-Renom MA, Beato M, le Dily F.
    On the demultiplexing of chromosome capture conformation data.
    On the demultiplexing of chromosome capture conformation data. FEBS Letters 589 3005-3013. 07/10/2015. F.I.:3.341
    [doi:10.1016/j.febslet.2015.05.049]
    Serra F, Di Stefano M, Spill YG, Cuartero Y, Goodstadt M, Baù D, Marti-Renom MA.
    Restraint-based three-dimensional modeling of genomes and genomic domains.
    Restraint-based three-dimensional modeling of genomes and genomic domains. FEBS Letters 589 2987-2995. 07/10/2015. F.I.:3.341
    [doi:10.1016/j.febslet.2015.05.012]
    Vicent GP, Wright RHG, Beato M.
    Linker histones in hormonal gene regulation.
    Linker histones in hormonal gene regulation. Biochimica et Biophysica Acta 1859 (2016) 520–525. 27/10/2015.
    [doi:10.1016/j.bbagrm.2015.10.016]