Journal
TRENDS IN IMMUNOLOGY
Volume 36, Issue 9, Pages 507-518Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2015.07.006
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Funding
- NCI NIH HHS [R01 CA173903] Funding Source: Medline
- NHLBI NIH HHS [K99 HL123485] Funding Source: Medline
- NIDDK NIH HHS [P01 DK074868, R01 DK091183] Funding Source: Medline
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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.
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