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Immunity. 2013 Jun 27;38(6):1271-84. doi: 10.1016/j.immuni.2013.05.011. Epub 2013 Jun 20.

Global chromatin state analysis reveals lineage-specific enhancers during the initiation of human T helper 1 and T helper 2 cell polarization.

Author information

1
Division of Medical Genetics and Department of Genome Sciences, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA. rdhawk@uw.edu

Abstract

Naive CD4⁺ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, we generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hr of in vitro polarization toward T helper 1 (Th1) and T helper 2 (Th2) cell lineages. Our analysis indicated that even at this very early time point, cell-specific gene regulation and enhancers were at work directing lineage commitment. Further examination of lineage-specific enhancers identified transcription factors (TFs) with known and unknown T cell roles as putative drivers of lineage-specific gene expression. Lastly, an integrative analysis of immunopathogenic-associated SNPs suggests a role for distal regulatory elements in disease etiology.

PMID:
23791644
PMCID:
PMC4607036
DOI:
10.1016/j.immuni.2013.05.011
[Indexed for MEDLINE]
Free PMC Article

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