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International Immunology Advance Access first published online on February 14, 2005
This version published online on February 18, 2005
International Immunology, 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
Received September 21, 2004
Accepted December 19, 2004

Article

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

Kai-Yin Chau 1, Andrea M. Keane-Myers 2, Monica Fedele 3, Yasuhiro Ikeda 4, Remi J. Creusot 4, Lisa Menozzi 1, David J. Cousins 5, Guidalberto Manfioletti 6, Lionel Feigenbaum 7, Alfredo Fusco 3, and Santa Jeremy Ono 1*

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

* To whom correspondence should be addressed.
Santa Jeremy Ono, E-mail: santa.ono{at}ucl.ac.uk


  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.

Keywords: gene regulation; HMGA1; IFN-{gamma}.
The title has been corrected.
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