title: Global chromatin state analysis reveals lineage-specific enhancers during the initiation of human T helper 1 and T helper 2 cell polarization.
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.
authors.affiliation: 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
authors.forename: R David
authors.initials: RD
authors.lastname: Hawkins
authors.forename: Antti
authors.initials: A
authors.lastname: Larjo
authors.forename: Subhash K
authors.initials: SK
authors.lastname: Tripathi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wagner
authors.forename: Ying
authors.initials: Y
authors.lastname: Luu
authors.forename: Tapio
authors.initials: T
authors.lastname: Lönnberg
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Raghav
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Lee
authors.forename: Riikka
authors.initials: R
authors.lastname: Lund
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018417:Th1 Cells / Q000276:immunology*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D002843:Chromatin; D006657:Histones