Chromosome conformation capture

Chromosome conformation capture technologies

Chromosome conformation capture techniques (often abbreviated to 3C technologies or 3C-based methods[1]) are a set of molecular biology methods used to analyze the spatial organization of chromatin in a cell. These methods quantify the number of interactions between genomic loci that are nearby in 3-D space, but may be separated by many nucleotides in the linear genome.[2] Such interactions may result from biological functions, such as promoter-enhancer interactions, or from random polymer looping, where undirected physical motion of chromatin causes loci to collide.[3] Interaction frequencies may be analyzed directly,[4] or they may be converted to distances and used to reconstruct 3-D structures.[5]

The chief difference between 3C-based methods is their scope. For example, when using PCR to detect interaction in a 3C experiment, the interactions between two specific fragments are quantified. In contrast, Hi-C quantifies interactions between all possible pairs of fragments simultaneously. Deep sequencing of material produced by 3C also produces genome-wide interactions maps.

  1. ^ de Wit E, de Laat W (January 2012). "A decade of 3C technologies: insights into nuclear organization". Genes & Development. 26 (1): 11–24. doi:10.1101/gad.179804.111. PMC 3258961. PMID 22215806.
  2. ^ Hakim O, Misteli T (March 2012). "SnapShot: Chromosome confirmation capture". Cell. 148 (5): 1068.e1–2. doi:10.1016/j.cell.2012.02.019. PMC 6374129. PMID 22385969.
  3. ^ Ay F, Bailey TL, Noble WS (June 2014). "Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts". Genome Research. 24 (6): 999–1011. doi:10.1101/gr.160374.113. PMC 4032863. PMID 24501021.
  4. ^ Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Aiden EL (December 2014). "A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping". Cell. 159 (7): 1665–80. doi:10.1016/j.cell.2014.11.021. PMC 5635824. PMID 25497547.
  5. ^ Varoquaux N, Ay F, Noble WS, Vert JP (June 2014). "A statistical approach for inferring the 3D structure of the genome". Bioinformatics. 30 (12): i26–33. doi:10.1093/bioinformatics/btu268. PMC 4229903. PMID 24931992.

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