Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T helper 1 and T helper 2 Cell Polarization

• The first genome-wide maps of enhancer elements used in early Th1 and Th2 cell-lineage commitment
• Lineage-specific enhancers are mapped to nucleosome-free resolution
• Enhancers overlap SNPs associated with autoimmune disorders
• SNPs often occur at enhancers within TF binding-site motifs

SummaryNaive 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.

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