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Trends Immunol. 2015 Sep;36(9):507-18. doi: 10.1016/j.it.2015.07.006. Epub 2015 Aug 19.

Exploiting genomics and natural genetic variation to decode macrophage enhancers.

Author information

1
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
2
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA; Faculty of Biology, Department II, Ludwig-Maximilians Universität München, Planegg-Martinsried 85152, Germany.
3
Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
4
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA. Electronic address: ckg@ucsd.edu.

Abstract

The mammalian genome contains on the order of a million enhancer-like regions that are required to establish the identities and functions of specific cell types. Here, we review recent studies in immune cells that have provided insight into the mechanisms that selectively activate certain enhancers in response to cell lineage and environmental signals. We describe a working model wherein distinct classes of transcription factors define the repertoire of active enhancers in macrophages through collaborative and hierarchical interactions, and discuss important challenges to this model, specifically providing examples from T cells. We conclude by discussing the use of natural genetic variation as a powerful approach for decoding transcription factor combinations that play dominant roles in establishing the enhancer landscapes, and the potential that these insights have for advancing our understanding of the molecular causes of human disease.

PMID:
26298065
PMCID:
PMC4548828
DOI:
10.1016/j.it.2015.07.006
[Indexed for MEDLINE]
Free PMC Article

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