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International Immunology Advance Access originally published online on February 14, 2005
International Immunology 2005 17(3):297-306; doi:10.1093/intimm/dxh209
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

IFN-{gamma} gene expression is controlled by the architectural transcription factor HMGA1

Kai-Yin Chau1, Andrea M. Keane-Myers2, Monica Fedele3, Yasuhiro Ikeda4, Remi J. Creusot4, Lisa Menozzi1, David J. Cousins5, Guidalberto Manfioletti6, Lionel Feigenbaum7, Alfredo Fusco3 and Santa Jeremy Ono1

1 Department of Immunology, Institute of Ophthalmology, University College London and Moorfields Eye Hospital, NHS Foundation Trust, 11-43 Bath Street, London EC1V 9EL, UK
2 Laboratory of Allergic Diseases, Eosinophil Biology Section, NIAID, NIH, Rockville, MD, USA
3 Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia e Oncologia Sperimentale del CNR, University of Naples "Federico II", Italy
4 Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, UK
5 Department of Asthma, Allergy & Respiratory Science, GKT School of Medicine, King's College London, UK
6 Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Università di Trieste, Italy
7 Science Applications International Corporation, NCI, Frederick, MD, USA

Correspondence to: S. J. Ono; E-mail: santa.ono{at}ucl.ac.uk

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.

Keywords: gene regulation, HMGA1, IFN-{gamma}

Transmitting editor: F. S. Rosen


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