Structural Genomics @CNAG CRG


DNA

The three-dimensional organization of the genome plays important, yet poorly understood roles in gene regulation. First, gene expression involves formation of chromatin loops driven by physical interactions between promoters and distal regulatory elements. Second, active and inactive segments of the genome appear spatially separated from each other, which may contribute to their coordinated expression and silencing, respectively. Finally, formation of complex higher order chromosome structures plays critical roles in chromosome condensation and segregation during mitosis and meiosis. Thus, chromosomes assume multiple distinct conformations in relation to the expression status of resident genes, and undergo dramatic alterations in higher-order structure through the cell cycle.

Detailed insights into chromosome conformation will greatly contribute to a more complete characterization of genome regulation. The spatial organization of chromosomes is reflected in, and driven by, cis- and trans interactions between genomic elements. For instance, enhancers directly touch target genes resulting in the formation of intra- and inter-chromosomal loops. We have recently developed a hybrid method (computational and experimental) based on the hypothesis that the spatial conformation of chromosomes can be determined by using comprehensive in vivo chromatin interaction data sets and microscopy images. We apply and use those technologies together with our TADbit and TADdyn software to determine the higher-order chromatin folding of genomic domains and whole genomes.

Selected articles

Galan, S.,  Machnik, N.,  Kruse, K.,  Daz, N.,  Marti-Renom, M.A. and Vaquerizas, J.M.
"Quantitative comparison and feature extraction for chromatin contact data using structural similarity"
Nature Genetics (2020) doi:10.1038/s41588-0   
  
Nguyen, H.Q.,  Chattoraj, S.,  Castillo, D.,  Nguyen, S.C.,  Nir, G.,  Martins, N.M.C.,  Reginato, P.R.,  Hannan, M.,  Church, G.M.,  Daugharthy, E.R.,  Marti-Renom, M.A. and Wu, C.T.
"3D mapping and accelerated super-resolution imaging of the human genome using in situ sequencing"
Nature Methods (2020) 17 822832  
  
Soler-Vila, P.,  Cusco Pons, P.,  Farabella, I.,  Di Stefano, M. and Marti-Renom, M.A.
"Hierarchical chromatin organization detected by TADpole."
Nucleic Acids Research (2020) 48 (7) e39  
  
Di Stefano, M.,  Stadhouders, R.,  Farabella, I.,  Castillo, D.,  Serra, F.,  Graf, T. and Marti-Renom, M.A.
"Dynamic simulations of transcriptional control during cell reprogramming reveal spatial chromatin caging."
Nature Communications (2020) 11 2564  
  
Serra, F.,  Ba, D.,  Goodstadt, M.,  Castillo, D.,  Filion, F. and Marti-Renom, M.A.
"Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors"
PLOS Computational Biology (2017) 13(7) e1005665  
  

Grants

International. European Commission. H2020-ETN. 2019-2023 [8133278].
ChromDesign.
Catalonia. AGAUR. Suport a Grups de Recerca. 2018-2020 [SGR-468].
Structural Genomics.
Spain. MINECO. Plan Nacional. 2018-2021 [BFU2017-85926-P].
Structural analysis of genomes and genomic domains.
International. ERC. Synergy Grant. 2014-2020 [ERC-2013-SyG/609989].
Dynamics of human genome architecture in stable and transient gene expression changes.
Catalonia. La Marató de TV3. Grants 2016. 2017-2020 [320/C/2016].
Modeling three-dimensional chromosomal structure in beta cells to identify genetic mechanisms underlying type 2 diabetes.
International. European Commission. H2020 e-Infra. 2015-2018 [676556].
Multi-Scale Complex Genomics.
Spain. MINECO. Plan Nacional. 2014-2017 [BFU2013-47736].
Determining the three-dimensional structure of genomes and genomic domains.
International. HFSP. Grant program. 2012-2015 [RGP0044/2011].
Conformational changes of chromosomes during the cell cycle.
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