Abstract

The T-helper-cell 1 and 2 (T_H1 and T_H2) pathways, defined by cytokines interferon- (IFN-) and interleukin-4 (IL-4), respectively, comprise two alternative CD4⁺ T-cell fates, with functional consequences for the host immune system. These cytokine genes are encoded on different chromosomes. The recently described T_H2 locus control region (LCR) coordinately regulates the T_H2 cytokine genes by participating in a complex between the LCR and promoters of the cytokine genes Il4, Il5 and Il13. Although they are spread over 120 kilobases, these elements are closely juxtaposed in the nucleus in a poised chromatin conformation. In addition to these intrachromosomal interactions, we now describe interchromosomal interactions between the promoter region of the IFN- gene on chromosome 10 and the regulatory regions of the T_H2 cytokine locus on chromosome 11. DNase I hypersensitive sites that comprise the T_H2 LCR developmentally regulate these interchromosomal interactions. Furthermore, there seems to be a cell-type-specific dynamic interaction between interacting chromatin partners whereby interchromosomal interactions are apparently lost in favour of intrachromosomal ones upon gene activation. Thus, we provide an example of eukaryotic genes located on separate chromosomes associating physically in the nucleus via interactions that may have a function in coordinating gene expression.

1. Section of Immunobiology, and
2. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
3. The Howard Hughes Medical Institute, New Haven, Connecticut 06520, USA
4. *These authors contributed equally to this work

Correspondence to: Richard A. Flavell^1,3 Correspondence and requests for materials should be addressed to R.A.F. (Email: richard.flavell@yale.edu).

Received 11 February 2005; Accepted 30 March 2005

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