Unconventional association of the polycomb group proteins with cytokine genes in differentiated T helper cells

Eyal Jacob, Reut Hod-Dvorai, Sagie Schif-Zuck, Orly Avni

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The cytokine transcription profiles of developing T helper 1 and T helper 2 cells are imprinted and induced appropriately following stimulation of differentiated cells. Epigenetic regulation combines several mechanisms to ensure the inheritance of transcriptional programs. We found that the expression of the polycomb group proteins, whose role in maintaining gene silencing is well documented, was induced during development in both T helper lineages. Nevertheless, the polycomb proteins, YY1, Mel-18, Ring1A, Ezh2, and Eed, bound to the Il4 and Ifng loci in a differential pattern. In contrast to the prevailing dogma, the binding activity of the polycomb proteins in differentiated T helper cells was associated with cytokine transcription. The polycomb proteins bound to the cytokine genes under resting conditions, and their binding was induced dynamically following stimulation. The recruitment of the polycomb proteins Mel-18 and Ezh2 to the cytokine promoters was inhibited in the presence of cyclosporine A, suggesting the involvement of NFAT. Considering their binding pattern at the cytokine genes and their known function in higher order folding of regulatory elements, we propose a model whereby the polycomb proteins, in some contexts, positively regulate gene expression by mediating long-distance chromosomal interactions.

Original languageEnglish
Pages (from-to)13471-13481
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - 9 May 2008
Externally publishedYes

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