Abstract
The chromosome conformation capture (3C) method has been invaluable in studying chromatin interactions in a population of cells at a resolution surpassing that of light microscopy, for example in the detection of functional contacts between enhancers and promoters. Recent developments in sequencing-based chromosomal contact mapping (Hi-C, 5C and 4C-Seq) have allowed researchers to interrogate pairwise chromatin interactions on a wider scale, shedding light on the three-dimensional organization of chromosomes. These methods present significant technical and bioinformatic challenges to consider at the start of the project. Here, we describe two alternative methods for Hi-C, depending on the size of the genome, and discuss the major computational approaches to convert the raw sequencing data into meaningful models of how genomes are organized.
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References
Lanctot C, Cheutin T, Cremer M et al (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 8:104–115
Dekker J, Rippe K, Dekker M et al (2002) Capturing chromosome conformation. Science 295:1306–1311
Thierry Forne’s chapter in this same book…
Dekker J, Marti-Renom MA, Mirny LA (2013) Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nat Rev Genet 14:390–403
Lieberman-Aiden E, van Berkum NL, Williams L et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293
Dixon JR, Selvaraj S, Yue F et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–380
Sexton T, Yaffe E, Kenigsberg E et al (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148:458–472
Seitan VC, Faure AJ, Zhan Y et al (2013) Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Genome Res 23:2066–2077
Sofueva S, Yaffe E, Chan WC et al (2013) Cohesin-mediated interactions organize chromosomal domain architecture. EMBO J 32:3119–3129
Zuin J, Dixon JR, van der Reijden MI et al (2014) Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci U S A 111:996–1001
van de Werken HJ, Landan G, Holwerda SJ et al (2012) Robust 4C-seq data analysis to screen for regulatory DNA interactions. Nat Methods 9:969–972
Yaffe E, Tanay A (2011) Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture. Nat Genet 43:1059–1065
Schoenfelder S, Sexton T, Chakalova L et al (2010) Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat Genet 42:53–61
Raab JR, Chiu J, Zhu J et al (2012) Human tRNA genes function as chromatin insulators. EMBO J 31:330–350
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Vietri Rudan, M., Hadjur, S., Sexton, T. (2016). Detecting Spatial Chromatin Organization by Chromosome Conformation Capture II: Genome-Wide Profiling by Hi-C. In: Haggarty, P., Harrison, K. (eds) Population Epigenetics. Methods in Molecular Biology, vol 1589. Humana Press, New York, NY. https://doi.org/10.1007/7651_2015_261
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DOI: https://doi.org/10.1007/7651_2015_261
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Publisher Name: Humana Press, New York, NY
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Online ISBN: 978-1-4939-6903-6
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