title: IFN-gamma gene expression is controlled by the architectural transcription factor HMGA1.
abstract: We report for the first time that IFNG gene expression requires high mobility group (HMG)A1, the architectural transcription factor mediating enhanceosome formation. This finding is supported by our direct studies of T cells isolated from the HMGA1-transgenic mice displaying an up-regulation of IFN-gamma production and of HMGA1-deficient mice exhibited a decreased IFN-gamma induction. In parallel transfection studies in EL4 cells, we observed elevated IFNG gene promoter activity in cells stably over-expressing HMGA1 and a reduction of such activity in cells expressing dominant-negative HMGA1. In vitro binding assays further demonstrated a specific interaction of HMGA1 to defined regions of the IFNG gene proximal promoter.
authors.affiliation: Department of Immunology, Institute of Ophthalmology, University College London and Moorfields Eye Hospital, NHS Foundation Trust, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Chau
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Keane-Myers
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Remi J
authors.initials: RJ
authors.lastname: Creusot
authors.forename: Lisa
authors.initials: L
authors.lastname: Menozzi
authors.forename: David J
authors.initials: DJ
authors.lastname: Cousins
authors.forename: Guidalberto
authors.initials: G
authors.lastname: Manfioletti
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.forename: Santa Jeremy
authors.initials: SJ
authors.lastname: Ono
mesh_terms: D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D024003:HMGA Proteins / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D024003:HMGA Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D007371:Interferon-gamma