Molecular mechanisms by which T-bet regulates T-helper cell commitment

Academic Article


  • 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. © 2010 John Wiley & Sons A/S.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Miller SA; Weinmann AS
  • Start Page

  • 233
  • End Page

  • 246
  • Volume

  • 238
  • Issue

  • 1