Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions

Zhihu Zhao, Gholamreza Tavoosidana, Mikael Sjölinder, Anita Göndör, Piero Mariano, Sha Wang, Chandrasekhar Kanduri, Magda Lezcano, Kuljeet Singh Sandhu, Umashankar Singh, Vinod Pant, Vijay Tiwari, Sreenivasulu Kurukuti, Rolf Ohlsson

Research output: Contribution to journalArticle

609 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1341-1347
Number of pages7
JournalNature Genetics
Volume38
Issue number11
DOIs
Publication statusPublished - 23 Nov 2006

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