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The three 'C' s of chromosome conformation capture: controls, controls, controls

Abstract

Transcription regulation in higher eukaryotes is controlled by regulatory elements such as enhancers that are recognized by transcription factors. In many cases regulatory elements can be located at distances up to several megabases from their target genes1,2. Recent evidence shows that long-range control of gene expression can be mediated through direct physical interactions between genes and these regulatory elements. Such looping interactions can be detected using the chromosome conformation capture (3C) methodology3. Although 3C is experimentally straightforward, to draw meaningful conclusions one must carefully design 3C experiments and implement the conscientious use of controls. The general guidelines presented here should help experimental design and minimize misinterpretation of 3C experiments.

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Figure 1: Interacting genetic elements can be detected by the 3C assay.
Figure 2: Examples of 3C analyses.

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Acknowledgements

I acknowledge members of the Dekker lab, M. Walhout and J. Perry, for discussions and critical reading of the manuscript. Research in the Dekker lab is supported by a grant from the National Institutes of Health (HG03143).

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Correspondence to Job Dekker.

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Dekker, J. The three 'C' s of chromosome conformation capture: controls, controls, controls. Nat Methods 3, 17–21 (2006). https://doi.org/10.1038/nmeth823

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