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Human enhancers harboring specific sequence composition, activity, and genome organization are linked to the immune response

View ORCID ProfileCharles-Henri Lecellier, View ORCID ProfileWyeth W. Wasserman, View ORCID ProfileAnthony Mathelier
doi: https://doi.org/10.1101/078477
Charles-Henri Lecellier
1Institut de Gntique Molculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France
2Institut de Biologie Computationnelle, 860 rue de St. Priest, 34095 Montpellier cedex 5, France
3Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Room 3103, V5Z 4H4, Vancouver, BC, Canada
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  • For correspondence: charles.lecellier@igmm.cnrs.fr anthony.mathelier@ncmm.uio.no
Wyeth W. Wasserman
3Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Room 3103, V5Z 4H4, Vancouver, BC, Canada
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Anthony Mathelier
3Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Room 3103, V5Z 4H4, Vancouver, BC, Canada
4Centre for Molecular Medicine Norway (NCMM), Nordic EMBL partnership, Faculty of Medicine, University of Oslo, Oslo, Norway
5Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
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  • For correspondence: charles.lecellier@igmm.cnrs.fr anthony.mathelier@ncmm.uio.no
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Abstract

The FANTOM5 consortium recently characterized 65,423 human enhancers from 1,829 cell and tissue samples using the Cap Analysis of Gene Expression technology. We showed that the guanine and cytosine content at enhancer regions distinguishes two classes of enhancers harboring distinct DNA structural properties at flanking regions. A functional analysis of their predicted gene targets highlighted one class of enhancers as significantly enriched for associations with immune response genes. Moreover, these enhancers were specifically enriched for regulatory motifs recognized by TFs involved in immune response. We observed that enhancers enriched for links to immune response genes were more cell type specific, preferentially activated upon bacterial infection, and with specific response activity. Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically-associated domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.

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Posted May 18, 2018.
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Human enhancers harboring specific sequence composition, activity, and genome organization are linked to the immune response
Charles-Henri Lecellier, Wyeth W. Wasserman, Anthony Mathelier
bioRxiv 078477; doi: https://doi.org/10.1101/078477
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Human enhancers harboring specific sequence composition, activity, and genome organization are linked to the immune response
Charles-Henri Lecellier, Wyeth W. Wasserman, Anthony Mathelier
bioRxiv 078477; doi: https://doi.org/10.1101/078477

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