title: Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells.
abstract: Epigenetic modifications, such as posttranslational modifications of histones, play an important role in gene expression and regulation. These modifications are in part mediated by the Trithorax group (TrxG) complex and the Polycomb group (PcG) complex, which activate and repress transcription, respectively. We herein investigate the role of Menin, a component of the TrxG complex in T helper (Th) cell differentiation and show a critical role for Menin in differentiation and maintenance of Th17 cells. Menin(-/-) T cells do not efficiently differentiate into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro cultures. Menin deficiency resulted in the attenuation of Th17-induced airway inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a gene locus and was required for the deposition of permissive histone modifications and recruitment of the RNA polymerase II transcriptional complex. Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for the induction of Rorc expression and permissive histone modifications in differentiating Th17 cells. In contrast, Menin was required to maintain expression of Rorc in differentiated Th17 cells, indicating that Menin is essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression.
authors.affiliation: Departments of Immunology.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Departments of Immunology.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Onodera
authors.affiliation: Departments of Immunology.
authors.forename: Urara
authors.initials: U
authors.lastname: Kanai
authors.affiliation: Departments of Immunology.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Departments of Immunology.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata-Ninomiya
authors.affiliation: Departments of Immunology.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Wada
authors.affiliation: Departments of Immunology.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kiuchi
authors.affiliation: Departments of Immunology.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.affiliation: Departments of Immunology.
authors.forename: Damon J
authors.initials: DJ
authors.lastname: Tumes
authors.affiliation: Departments of Immunology.
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Departments of Immunology.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yagi
authors.affiliation: Medical Immunology, and.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.affiliation: Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; and.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.affiliation: Departments of Immunology, Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Chiba 260-8670, Japan tnakayama@faculty.chiba-u.jp.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002843:Chromatin / Q000276:immunology / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D011495:Histone-Lysine N-Methyltransferase / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051788:Myeloid-Lymphoid Leukemia Protein / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012319:RNA Polymerase II / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D002843:Chromatin; C098680:Il17a protein, mouse; D020381:Interleukin-17; C484898:Men1 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011518:Proto-Oncogene Proteins; C539901:Rorc protein, mouse; D051788:Myeloid-Lymphoid Leukemia Protein; D010047:Ovalbumin; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; D012319:RNA Polymerase II
keywords: RNAPII; asthma; chromatin