GTF2IRD1 regulates transcription by binding an evolutionarily conserved DNA motif ‘GUCE’

Thompson, P.D.; Webb, M.; Beckett, W.; Hinsley, T.; Jowitt, T.; Sharrocks, A.D.; Tassabehji, M.

doi:10.1016/j.febslet.2007.02.040

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Volume 581, Issue 6 , Pages 1233-1242, 20 March 2007

GTF2IRD1 regulates transcription by binding an evolutionarily conserved DNA motif ‘GUCE’

Edited by Ivan Sadowski

P.D. Thompson
- Academic Unit of Medical Genetics, The University of Manchester, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK
M. Webb
- Academic Unit of Medical Genetics, The University of Manchester, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK
W. Beckett
- Academic Unit of Medical Genetics, The University of Manchester, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK
T. Hinsley
- Academic Unit of Medical Genetics, The University of Manchester, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK
T. Jowitt
- School of Life Sciences, The University of Manchester, Manchester, UK
A.D. Sharrocks
- School of Life Sciences, The University of Manchester, Manchester, UK
M. Tassabehji
- Academic Unit of Medical Genetics, The University of Manchester, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK
- Corresponding author. Fax: +44 0 161 276 6606.

Received 26 October 2006; received in revised form 14 February 2007; accepted 16 February 2007. published online 01 March 2007.

Abstract

GTF2IRD1 is a member of a family of transcription factors whose defining characteristic is varying numbers of a helix–loop–helix like motif, the I-repeat. Here, we present functional analysis of human GTF2IRD1 in regulation of three genes (HOXC8, GOOSECOID and TROPONIN I_SLOW). We define a regulatory motif (GUCE–GTF2IRD1 Upstream Control Element) common to all three genes. GUCE is bound in vitro by domain I-4 of GTF2IRD1 and mediates transcriptional regulation by GTF2IRD1 in vivo. Definition of this site will assist in identification of other downstream targets of GTF2IRD1 and elucidation of its role in the human developmental disorder Williams–Beuren syndrome.

Keywords: GTF2IRD1, TFII-I, GUCE, Transcription regulation, Williams–Beuren syndrome, DNA binding, isoforms