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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Chromatin / metabolism*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Immune System Diseases / genetics
  • Immune System Diseases / immunology*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Th1 Cells / immunology*
  • Th1-Th2 Balance
  • Th2 Cells / immunology*


  • Chromatin
  • Histones