Interchromosomal associations between alternatively expressed loci

Charalampos G. Spilianakis, Maria D. Lalioti, Terrence Town, Gap Ryol Lee and Richard A. Flavell ()
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Charalampos G. Spilianakis: Section of Immunobiology
Maria D. Lalioti: Yale University School of Medicine
Terrence Town: Section of Immunobiology
Gap Ryol Lee: Section of Immunobiology
Richard A. Flavell: Section of Immunobiology

Nature, 2005, vol. 435, issue 7042, 637-645

Abstract: Abstract The T-helper-cell 1 and 2 (TH1 and TH2) pathways, defined by cytokines interferon-γ (IFN-γ) 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 TH2 locus control region (LCR) coordinately regulates the TH2 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-γ gene on chromosome 10 and the regulatory regions of the TH2 cytokine locus on chromosome 11. DNase I hypersensitive sites that comprise the TH2 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.

Date: 2005
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DOI: 10.1038/nature03574

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