Nature Genetics
- 38, 1341 - 1347 (2006)
Published online: 8 October 2006; | doi:10.1038/ng1891
Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactionsZhihu Zhao1, 2, Gholamreza Tavoosidana1, 2, Mikael Sjölinder1, Anita Göndör1, Piero Mariano1, Sha Wang1, Chandrasekhar Kanduri1, Magda Lezcano1, Kuljeet Singh Sandhu1, Umashankar Singh1, Vinod Pant1, Vijay Tiwari1, Sreenivasulu Kurukuti1 & Rolf Ohlsson11
Department of Development & Genetics, Evolution Biology Centre, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden. 2
These authors contributed equally to the work.
Correspondence should be addressed to rolf.ohlsson@ebc.uu.se Accumulating evidence converges on the possibility that chromosomes interact with each other to regulate transcription in trans. To systematically explore the epigenetic dimension of such interactions, we devised a strategy termed circular chromosome conformation capture (4C). This approach involves a circularization step that enables high-throughput screening of physical interactions between chromosomes without a preconceived idea of the interacting partners. Here we identify 114 unique sequences from all autosomes, several of which interact primarily with the maternally inherited H19 imprinting control region. Imprinted domains were strongly overrepresented in the library of 4C sequences, further highlighting the epigenetic nature of these interactions. Moreover, we found that the direct interaction between differentially methylated regions was linked to epigenetic regulation of transcription in trans. Finally, the patterns of interactions specific to the maternal H19 imprinting control region underwent reprogramming during in vitro maturation of embryonic stem cells. These observations shed new light on development, cancer epigenetics and the evolution of imprinting.
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