title: Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation.
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.
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Qingtian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Jia
authors.initials: J
authors.lastname: Zou
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Xilai
authors.initials: X
authors.lastname: Ding
authors.affiliation: Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Iouri
authors.initials: I
authors.lastname: Chepelev
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Xikun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892.
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000166:cytology / Q000201:enzymology; D058504:Th17 Cells / Q000166:cytology / Q000201:enzymology; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse