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- Title
Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction.
- Authors
Mullen, Alan C; Hutchins, Anne S; High, Frances A; Lee, Hubert W; Sykes, Kara J; Chodosh, Lewis A; Reiner, Steven L
- Abstract
Type 1 helper T (T(H)1) cells are essential for cellular immunity, but their ontogeny, maturation and durability remain poorly understood. By constructing a dominant-negative form of T-bet, we were able to determine the role played by this lineage-inducing trans-activator in the establishment and maintenance of heritable T(H)1 gene expression. Optimal induction of interferon-gamma (IFN-gamma) expression required genetic interaction between T-bet and its target, the homeoprotein Hlx. In fully mature T(H)1 cells, reiteration of IFN-gamma expression and stable chromatin remodeling became relatively independent of T-bet activity and coincided with demethylation of DNA. In contrast, some lineage attributes, such as expression of IL-12R beta 2 (interleukin 12 receptor beta 2), required ongoing T-bet activity in mature T(H)1 cells and their progeny. These findings suggest that heritable states of gene expression might be maintained by continued expression of the inducing factor or by a mechanism that confers a stable imprint of the induced state.
- Publication
Nature immunology, 2002, Vol 3, Issue 7, p652
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni807