Molecular mechanisms by which T-bet regulates T-helper cell commitment.
Current research suggests that a number of newly identified T-helper cell subsets retain a degree of context-dependent plasticity in their signature cytokine expression patterns. To understand this process, a major challenge is to determine the molecular mechanisms by which lineage-defining transcription factors regulate gene expression profiles in T-helper cells. This mechanistic information will aid in our interpretation of whether a T-helper cell state that expresses or retains the capacity to re-express a combination of lineage-defining transcription factors will have a stable or more flexible gene expression profile. Studies examining the developmental T-box transcription factor T-bet demonstrate the powerful information that is gained from combining in vivo analysis with basic biochemical and molecular mechanism approaches. Significantly, T-bet's ability to physically recruit epigenetic modifying complexes, in particular a Jmjd3 H3K27-demethylase and a Set7/9 H3K4-methyltransferase complex, to its target genes allows T-bet to effectively reverse and establish new epigenetic states. This observation suggests that until T-bet is permanently extinguished, T-helper cells will retain some plasticity toward a T-helper 1-like program. Therefore, insight into the complexity of T-helper cell commitment decisions will be aided by determining the molecular mechanisms for lineage-defining transcription factors.
Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
Sara A
SA
Miller
Amy S
AS
Weinmann
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D044127:Epigenesis, Genetic / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D056466:Histone Demethylases / Q000276:immunology*; D011495:Histone-Lysine N-Methyltransferase / Q000276:immunology*; D006801:Humans; D020825:T-Box Domain Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase