Hlx is induced by and genetically interacts with T-bet to promote heritable T_H1 gene induction.

Mullen, Alan C.; Hutchins, Anne S.; High, Frances A.; Lee, Hubert W.; Sykes, Kara J.; Chodosh, Lewis A.; Reiner, Steven L.

Type I helper T (T[sub H]I) 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[sub H]I gene expression. Optimal induction of interferon-γ (IFN-γ) expression required genetic interaction between T-bet and its target, the homeoprotein HIx. In fully mature T[sub H]I cells, reiteration of IFN-γ 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-12Rβ2 (interleukin 12 receptor β2), required ongoing T-bet activity in mature T[sub H]I 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.

CELLULAR immunity; GENETIC transcription

Nature Immunology, 2002, Vol 3, Issue 7, p652

1529-2908

Academic Journal

10.1038/ni807