IFN-gamma gene expression is controlled by the architectural transcription factor HMGA1.
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.
Chau
Kai-Yin
KY
Department of Immunology, Institute of Ophthalmology, University College London and Moorfields Eye Hospital, NHS Foundation Trust, 11-43 Bath Street, London EC1V 9EL, UK.
Keane-Myers
Andrea M
AM
Fedele
Monica
M
Ikeda
Yasuhiro
Y
Creusot
Remi J
RJ
Menozzi
Lisa
L
Cousins
David J
DJ
Manfioletti
Guidalberto
G
Feigenbaum
Lionel
L
Fusco
Alfredo
A
Ono
Santa Jeremy
SJ
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
D024003:HMGA Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D007371:Interferon-gamma