title: Domain analyses of the Runx1 transcription factor responsible for modulating T-cell receptor-beta/CD4 and interleukin-4/interferon-gamma expression in CD4(+) peripheral T lymphocytes.
abstract: The Runx1 transcription factor is one of the master regulators of T-lymphocyte differentiation. There have been several reports trying to assign a domain within the Runx1 protein that is responsible for gene expression in thymocytes. The Runx1 domains involved in regulating the expression of several genes in peripheral CD4(+) T cells were analysed. It was observed that Runx1 over-expression enhanced the surface expression of CD4 and CD69 molecules via its activation domain and VWRPY domain, and decreased that of T-cell receptor-beta via its activation domain. Runx1 over-expression enhanced interferon-gamma expression via its activation and VWRPY domains, and abolished interleukin-4 expression through its activation domain. Transduction of Runx1 did not down-regulate CD4 expression until 72 hr of culture, but the repression of CD4 expression became evident after 96 hr. The main region responsible for repressing CD4 expression was the inhibitory domain of Runx1. Taken together, these results lead to a proposal that the regions in Runx1 responsible for modulating gene expression are distinct in thymocytes and in peripheral CD4(+) T cells.
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging and Cancer, Graduate School of Life Science, Tohoku University, Sendai, Japan. utino@idac.tohoku.ac.jp
authors.forename: Ryuji
authors.initials: R
authors.lastname: Uchino
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000276:immunology; D017353:Gene Deletion; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D050676:Core Binding Factor Alpha 2 Subunit; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens; C493726:Runx1 protein, mouse
references.citation: Genes Cells. 1999 Dec;4(12):685-96
references.pmid: 10620014
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11590-5
references.pmid: 9751710
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7731-6
references.pmid: 12796513
references.citation: J Immunol. 1989 Aug 15;143(4):1123-8
references.pmid: 2501389
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):840-5
references.pmid: 17213321
references.citation: J Immunol. 2000 Dec 15;165(12):6816-24
references.pmid: 11120804
references.citation: J Exp Med. 2003 Jul 7;198(1):51-61
references.pmid: 12835475
references.citation: Eur J Immunol. 2005 Nov;35(11):3187-95
references.pmid: 16276482
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3062-6
references.pmid: 10716735
references.citation: Blood. 2004 Jan 15;103(2):562-70
references.pmid: 14504086
references.citation: Cell. 2002 Nov 27;111(5):621-33
references.pmid: 12464175
references.citation: Semin Immunol. 1999 Aug;11(4):283-92
references.pmid: 10441214
references.citation: Trends Genet. 1993 Oct;9(10):338-41
references.pmid: 8273148
references.citation: Mol Cell Biol. 2000 Jan;20(1):319-28
references.pmid: 10594034
references.citation: Curr Opin Genet Dev. 2003 Feb;13(1):43-7
references.pmid: 12573434
references.citation: J Immunol. 2001 Nov 1;167(9):4957-65
references.pmid: 11673502
references.citation: J Immunol. 1998 Aug 1;161(3):1194-203
references.pmid: 9686579
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6746-51
references.pmid: 9192636
references.citation: J Immunol. 2005 Mar 15;174(6):3526-33
references.pmid: 15749889
references.citation: J Immunol. 2002 Aug 15;169(4):1705-12
references.pmid: 12165490
references.citation: Mol Cell Biol. 1998 May;18(5):2444-54
references.pmid: 9566865
references.citation: Clin Chem. 1994 Nov;40(11 Pt 2):2128-31
references.pmid: 7955399
references.citation: Immunol Rev. 2004 Dec;202:203-22
references.pmid: 15546395
references.citation: Eur J Immunol. 2000 Sep;30(9):2639-49
references.pmid: 11009098
references.citation: Mol Cell Biol. 1993 Oct;13(10):6336-45
references.pmid: 8413232
references.citation: J Biol Chem. 1999 Oct 29;274(44):31577-82
references.pmid: 10531362
references.citation: J Exp Med. 2007 Aug 6;204(8):1945-57
references.pmid: 17646406
references.citation: Oncogene. 2004 Oct 18;23(48):7990-8000
references.pmid: 15489916
references.citation: Nature. 2007 Apr 5;446(7136):685-9
references.pmid: 17377532
references.citation: J Immunol. 2005 Oct 1;175(7):4475-82
references.pmid: 16177090
references.citation: Immunol Lett. 2003 Oct 9;89(1):39-46
references.pmid: 12946863
references.citation: Mol Cell Biol. 1997 Sep;17(9):5581-7
references.pmid: 9271433
references.citation: Mol Cell Biol. 1998 Jul;18(7):3915-25
references.pmid: 9632776
references.citation: J Virol. 1995 Aug;69(8):4941-9
references.pmid: 7609063
references.citation: J Exp Med. 2007 Aug 6;204(8):1749-55
references.pmid: 17646405
references.citation: J Immunol. 2004 Apr 1;172(7):4359-70
references.pmid: 15034051
references.citation: J Immunol. 2005 Mar 1;174(5):2627-36
references.pmid: 15728469
references.citation: EMBO J. 1998 Jun 1;17(11):2994-3004
references.pmid: 9606182