Chromatin three-dimensional interactions mediate genetic effects on gene expression

Author:

Delaneau O.123ORCID,Zazhytska M.4,Borel C.13ORCID,Giannuzzi G.4,Rey G.123ORCID,Howald C.123,Kumar S.56,Ongen H.123,Popadin K.467ORCID,Marbach D.68ORCID,Ambrosini G.56,Bielser D.1,Hacker D.9ORCID,Romano L.1,Ribaux P.1,Wiederkehr M.4,Falconnet E.1,Bucher P.56,Bergmann S.6810ORCID,Antonarakis S. E.13,Reymond A.4,Dermitzakis E. T.123ORCID

Affiliation:

1. Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.

2. Swiss Institute of Bioinformatics (SIB), University of Geneva, Geneva, Switzerland.

3. Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.

4. Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

5. Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

6. Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.

7. School of Life Science, Immanuel Kant Federal Baltic University, Kaliningrad, Russia.

8. Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.

9. Protein Expression Core Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

10. Computational Biology Division N1.05, Werner Beit North Faculty of Health Sciences, Cape Town, South Africa.

Abstract

Noncoding variation and gene expression Natural genetic variation outside of protein coding regions affects multiple molecular phenotypes that can differ across individuals. To examine how genomic variation affects proximal (cis) or distal (trans) gene regulation, Delaneau et al. analyzed gene expression, chromatin, and the three-dimensional conformation of the genome. Clustering regulatory elements and activity across individuals reveals genomic structures termed cis-regulatory domains and trans-regulatory hubs that affect gene expression. Associations between these structures and genes within and across chromosomes contribute to links between noncoding genetic variation and gene expression. Science , this issue p. eaat8266

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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