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Genetics. 2018 Aug;209(4):1055-1071. doi: 10.1534/genetics.118.301116. Epub 2018 Jun 5.

Human Enhancers Harboring Specific Sequence Composition, Activity, and Genome Organization Are Linked to the Immune Response.

Author information

1
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), 34293 Montpellier cedex5, France anthony.mathelier@ncmm.uio.no charles.lecellier@igmm.cnrs.fr.
2
Institut de Biologie Computationnelle, 34095 Montpellier, France.
3
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
4
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, V5Z 4H4, Canada anthony.mathelier@ncmm.uio.no charles.lecellier@igmm.cnrs.fr.
5
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, University of Oslo, 0349 Oslo, Norway.
6
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0372 Oslo, Norway.

Abstract

The FANTOM5 consortium recently characterized 65,423 human enhancers from 1829 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 transcription factors 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 associating 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.

KEYWORDS:

enhancer; immune response; sequence-level instructions; transcription

PMID:
29871881
PMCID:
PMC6063234
[Available on 2019-08-01]
DOI:
10.1534/genetics.118.301116
[Indexed for MEDLINE]

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