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Complex Multi‐Enhancer Contacts Captured By Genome Architecture Mapping, A Novel Ligation‐Free Approach
Author(s) -
Pombo Ana,
Beagrie Robert A,
Scialdone Antonio,
Schueler Markus,
Chotalia Mita,
Xie Sheila Q,
Kraemer Dorothee,
Santiago Ines,
Fraser James,
Dostie Josee,
Game Laurence,
Dillon Niall,
Edwards Paul AW,
Nicodemi Mario
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.99.3
Subject(s) - enhancer , genome , chromatin , chromosome conformation capture , computational biology , biology , gene , genetics , transcription factor
The organization of the genome in the nucleus and the interactions of genes with their regulatory elements are key elements of transcriptional control and their disruption causes disease. Technologies based on chromosome conformation capture (3C) have profoundly expanded our understanding of the role of genome architecture in gene regulation. However, 3C‐based techniques have important limitations, many of which arise from their reliance on digestion and ligation of the interacting DNA segments. We present a new genome‐wide method, Genome Architecture Mapping (GAM) for measuring three‐dimensional chromatin topology without ligation. We use this new method to generate a genome‐wide dataset of chromatin interactions in mouse ES cells, and compare to published Hi‐C data. GAM identifies specific chromatin contacts enriched for interactions between active genes and enhancers across very large genomic distances. GAM also reveals abundant three‐way contacts genome‐wide, especially between the enhancers most highly occupied by pluripotency transcription factors and highly transcribed genomic regions. These contacts are most prominent for sequences further away from the nuclear lamina. Our results shed light on a previously inaccessible complexity in genome architecture and a major role for gene‐expression specific contacts in organizing genome architecture of mammalian nuclei. Support or Funding Information The work was supported by the Medical Research Council, UK (AP, RAB, MC, SQX, IdS, LG, ND), by the MRC‐Technology (AP, MC), by the Helmholtz Foundation (AP, MS, MB, DK), by Breast Cancer Campaign (PAWE) and by Cancer Research UK (PAWE). Work by JD and JF was supported by grants from the Canadian Institutes of Health Research (CIHR) [MOP‐86716, CAP‐120350].