High-resolution analysis of cis -acting regulatory networks at the α-globin locus

Author:

Hughes Jim R.1,Lower Karen M.1,Dunham Ian2,Taylor Stephen3,De Gobbi Marco1,Sloane-Stanley Jacqueline A.1,McGowan Simon3,Ragoussis Jiannis4,Vernimmen Douglas1,Gibbons Richard J.1,Higgs Douglas R.1

Affiliation:

1. MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK

2. European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK

3. Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK

4. Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK

Abstract

We have combined the circular chromosome conformation capture protocol with high-throughput, genome-wide sequence analysis to characterize the cis -acting regulatory network at a single locus. In contrast to methods which identify large interacting regions (10–1000 kb), the 4C approach provides a comprehensive, high-resolution analysis of a specific locus with the aim of defining, in detail, the cis -regulatory elements controlling a single gene or gene cluster. Using the human α-globin locus as a model, we detected all known local and long-range interactions with this gene cluster. In addition, we identified two interactions with genes located 300 kb (NME4) and 625 kb (FAM173a) from the α-globin cluster.

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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