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Nature 462, 58-64 (5 November 2009) | doi:10.1038/nature08497; Received 25 July 2009; Accepted 11 September 2009

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An oestrogen-receptor-alpha-bound human chromatin interactome

Melissa J. Fullwood1, Mei Hui Liu1, You Fu Pan1, Jun Liu1, Han Xu1, Yusoff Bin Mohamed1, Yuriy L. Orlov1, Stoyan Velkov1, Andrea Ho1, Poh Huay Mei1, Elaine G. Y. Chew1, Phillips Yao Hui Huang1, Willem-Jan Welboren2, Yuyuan Han1, Hong Sain Ooi1, Pramila N. Ariyaratne1, Vinsensius B. Vega1, Yanquan Luo1, Peck Yean Tan1, Pei Ye Choy1, K. D. Senali Abayratna Wansa1, Bing Zhao1, Kar Sian Lim1, Shi Chi Leow1, Jit Sin Yow1, Roy Joseph1, Haixia Li1, Kartiki V. Desai1, Jane S. Thomsen1, Yew Kok Lee1, R. Krishna Murthy Karuturi1, Thoreau Herve1, Guillaume Bourque1, Hendrik G. Stunnenberg2, Xiaoan Ruan1, Valere Cacheux-Rataboul1, Wing-Kin Sung1,3, Edison T. Liu1, Chia-Lin Wei1, Edwin Cheung1,4,5 & Yijun Ruan1,4

  1. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672
  2. Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands
  3. Department of Computer Science, School of Computing, National University of Singapore, Singapore 117543
  4. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597
  5. School of Biological Sciences, Nanyang Technological University, Singapore 637551

Correspondence to: Edwin Cheung1,4,5Yijun Ruan1,4 Correspondence and requests for materials should be addressed to Y.R. (Email: ruanyj@gis.a-star.edu.sg) or E.C. (Email: cheungcwe@gis.a-star.edu.sg).

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Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor alpha (ER-alpha) in the human genome. We found that most high-confidence remote ER-alpha-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-alpha functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.