Transcription factor-dependent chromatin remodeling of Il18r1 during Th1 and Th2 differentiation.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Qing YuMark H Kaplan

Abstract

The IL-18Ralpha-chain is expressed on Th1 but not Th2 cells. We have recently shown that Stat4 is an important component of programming the Il18r1 locus (encoding IL-18Ralpha) for maximal expression in Th1 cells. Il18r1 is reciprocally repressed during Th2 development. In this report, we demonstrate the establishment of DH patterns that are distinct among undifferentiated CD4 T, Th1, and Th2 cells. Stat6 is required for the repression of Il18r1 expression and in Stat6-deficient Th2 cultures, mRNA levels, histone acetylation, and H3K4 methylation levels are intermediate between levels observed in Th1 and Th2 cells. Despite the repressive effects of IL-4 during Th2 differentiation, we observed only modest binding of Stat6 to the Il18r1 locus. In contrast, we observed robust GATA-3 binding to a central region of the locus where DNase hypersensitivity sites overlapped with conserved non-coding sequences in Il18r1 introns. Ectopic expression of GATA-3 in differentiated Th1 cells repressed Il18r1 mRNA and surface expression of IL-18Ralpha. These data provide further mechanistic insight into transcription factor-dependent establishment of Th subset-specific patterns of gene expression.

References

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Citations

Aug 28, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seth R GoodMark H Kaplan
Mar 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Herbert G KaslerEric Verdin
Dec 8, 2017·The Journal of Experimental Medicine·Jason S WeinsteinJoe Craft
Jul 9, 2020·Allergy, Asthma & Immunology Research·Mehmet KaracaRenato Polimanti
Oct 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hua-Chen ChangMark H Kaplan
Jun 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Duy PhamMark H Kaplan
Jun 12, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Duy PhamMark H Kaplan
May 23, 2014·Expert Opinion on Therapeutic Targets·Yan LiangDong-Qing Ye
May 9, 2019·Journal of Cellular Physiology·Aref HosseiniKamran Ghaedi
Jun 13, 2021·The Journal of Allergy and Clinical Immunology·Nao TanakaChikashi Terao

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