Format

Send to

Choose Destination
Nucleus. 2013 Sep-Oct;4(5):390-8. doi: 10.4161/nucl.26513. Epub 2013 Sep 18.

The statistical-mechanics of chromosome conformation capture.

Author information

1
Liggins Institute; University of Auckland; Auckland, New Zealand; Mathematics and Statistics; University of Otago; Dunedin, New Zealand; Institute of Natural and Mathematical Sciences; Massey University; Auckland, New Zealand; Deutsches Krebsforschungszentrum; Biophysics of Macromolecules; Heidelberg, Germany.

Abstract

Since Jacob and Monod's characterization of the role of DNA elements in gene control, it has been recognized that the linear organization of genome structure is important for the regulation of gene transcription and hence the manifestation of phenotypes. Similarly, it has long been hypothesized that the spatial organization (in three dimensions evolving through time), as part of the epigenome, makes a significant contribution to the genotype-phenotype transition. Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype. The apparent simplicity of these methodologies-crosslink chromatin, digest, dilute, ligate, detect interactions-belies the complexity of the data and the considerations that should be taken into account to ensure the generation and accurate interpretation of reliable data. Here we discuss the probabilistic nature of these methodologies and how this contributes to their endogenous limitations.

KEYWORDS:

chromosome conformation capture; chromosome organization; genome organization; proximity ligation

PMID:
24051548
PMCID:
PMC3899129
DOI:
10.4161/nucl.26513
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center