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Common themes emerge in the transcriptional control of T helper and developmental cell fate decisions regulated by the T‐box, GATA and ROR families
Author(s) -
Miller Sara A.,
Weinmann Amy S.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.03040.x
Subject(s) - biology , transcription factor , t helper cell , cell fate determination , genetics , gata transcription factor , t cell , cellular differentiation , rar related orphan receptor gamma , lineage (genetic) , effector , ets transcription factor family , gene , microbiology and biotechnology , immune system , gene expression , promoter
Summary Cellular differentiation requires the precise action of lineage‐determining transcription factors. In the immune system, CD4 + T helper cells differentiate into at least three distinct effector lineages, T helper type 1 (Th1), Th2 and Th17, with the fate of the cell at least in part determined by the transcription factors T‐box expressed in T cells (T‐bet), GATA‐3 and retinoid‐related orphan receptor γt (RORγt), respectively. Importantly, these transcription factors are members of larger families that are required for numerous developmental transitions from early embryogenesis into adulthood. Mutations in members of these transcription factor families are associated with a number of human genetic diseases due to a failure in completing lineage‐specification events when the factor is dysregulated. Mechanistically, there are both common and distinct functional activities that are utilized by T‐box, GATA and ROR family members to globally alter the cellular gene expression profiles at specific cell fate decision checkpoints. Therefore, understanding the molecular events that contribute to the ability of T‐bet, GATA‐3 and RORγt to define T helper cell lineages can provide valuable information relevant to the establishment of other developmental systems and, conversely, information from diverse developmental systems may provide unexpected insights into the molecular mechanisms utilized in T helper cell differentiation.