STANDARD_NAME	ONO_AML1_TARGETS_UP
SYSTEMATIC_NAME	M1977
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ONO_AML1_TARGETS_UP
NAMESPACE	MOUSE_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes up-regulated in CD4+ [GeneID=920] T lymphocytes by expression of AML1 [GeneID=861] off a viral vector.
DESCRIPTION_FULL	Naturally arising CD25+CD4+ regulatory T cells (T(R) cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy. T(R) cells specifically express the transcription factor Foxp3, a key regulator of T(R)-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and upregulate T(R)-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development, activates IL-2 and IFN-gamma gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural T(R) cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN-gamma production, upregulates T(R)-cell-associated molecules, and exerts suppressive activity. This transcriptional control of T(R)-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.
PMID	17377532
GEOID	
AUTHORS	Ono M,Yaguchi H,Ohkura N,Kitabayashi I,Nagamura Y,Nomura T,Miyachi Y,Tsukada T,Sakaguchi S
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Fig. S7: AML1, red
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	Ccnf,Cd244,CD38,Cxcr6,Ddx5,Dlk1,E2f1,Eomes,Fasl,Fos,Gadd45b,Gpr105,Gzma,Gzmc,Havcr2,Ifng,Jun,Mecp2,Nkg7,Pak1,Pdcd1,Pdcd1lg2,Rgs2,Sema4a,Slamf7
GENE_SYMBOLS	,CCNF,CD244,CXCR6,DDX5,DLK1,E2F1,EOMES,FASLG,FOS,GADD45B,P2RY14,GZMA,GZMB,HAVCR2,IFNG,JUN,MECP2,NKG7,PAK1,PDCD1,PDCD1LG2,RGS2,SEMA4A,SLAMF7
FOUNDER_NAMES