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Nat Commun. 2014 Dec 22;5:5780. doi: 10.1038/ncomms6780.

Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation.

Author information

1
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
2
Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
3
CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
4
Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892.
#
Contributed equally

Abstract

Epigenetic factors have been implicated in the regulation of CD4(+) T-cell differentiation. Jmjd3 plays a role in many biological processes, but its in vivo function in T-cell differentiation remains unknown. Here we report that Jmjd3 ablation promotes CD4(+) T-cell differentiation into Th2 and Th17 cells in the small intestine and colon, and inhibits T-cell differentiation into Th1 cells under different cytokine-polarizing conditions and in a Th1-dependent colitis model. Jmjd3 deficiency also restrains the plasticity of the conversion of Th2, Th17 or Treg cells to Th1 cells. The skewing of T-cell differentiation is concomitant with changes in the expression of key transcription factors and cytokines. H3K27me3 and H3K4me3 levels in Jmjd3-deficient cells are correlated with altered gene expression through interactions with specific transcription factors. Our results identify Jmjd3 as an epigenetic factor in T-cell differentiation via changes in histone methylation and target gene expression.

PMID:
25531312
PMCID:
PMC4274750
DOI:
10.1038/ncomms6780
[Indexed for MEDLINE]
Free PMC Article

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