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 throughput 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. Experimental data on chromosomal interactions can be obtained using a recently developed high-throughput technologies by the Dekker lab and other. We apply and use those technologies together with our TADbit software to determine the higher-order chromatin folding of genomic domains and whole genomes.

Selected articles

Serra, F.,  Bał, 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  
  
Trussart, M.,  Yus, E.,  Martinez, S.,  Bał, D.,  Tahara, Y.O.,  Pengo, T.,  Kretschmer, S.,  Swoger, J.,  Miyata, M.,  Marti-Renom, M.A.,  Lluch-Senar, M. and Serrano, L.
"Defined chromosome structure in a genome-reduced bacterium, Mycoplasma pneumoniae."
Nature Communications (2017) 8 14665  
  
Trussart, M.,  Serra, F.,  Bał, D.,  Junier, I.,  Serrano, L. and Marti-Renom, M.A.
"Assessing the limits of restraint-based 3D modeling of genomes and genomic domains."
Nucleic Acids Research (2015) 43 (7) 3465-3477  
  
Dekker, J.,  Marti-Renom, M.A. and Mirny, L.A.
"Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data"
Nature Reviews Genetics (2013) 14 390–403  
  
Bał, D.,  Sanyal, A.,  Lajoie, B.R.,  Capriotti, E.,   Byron, M.,   Lawrence J.B.,  Dekker, J. and Marti-Renom, M.A.
"The three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules"
Nature Structural and Molecular Biology (2011) 18 107-114  
  

Grants

Catalonia. La Marató de TV3. Grants 2016. 2017-2019 [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.
International. ERC. Synergy Grant. 2014-2019 [ERC-2013-SyG/609989].
Dynamics of human genome architecture in stable and transient gene expression changes.
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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