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Mcm1p-Induced DNA Bending Regulates the Formation of Ternary Transcription Factor Complexes

Fei-Ling Lim,^1,2, Andrew Hayes,² Adam G. West,^1, Aline Pic-Taylor,¹ Zoulfia Darieva,² Brian A. Morgan,¹ Stephen G. Oliver,² and Andrew D. Sharrocks^1,2*

Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH,¹ School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom²

Received 20 August 2002/ Returned for modification 30 September 2002/ Accepted 28 October 2002

The yeast MADS-box transcription factor Mcm1p plays an important regulatory role in several diverse cellular processes. In common with a subset of other MADS-box transcription factors, Mcm1p elicits substantial DNA bending. However, the role of protein-induced bending by MADS-box proteins in eukaryotic gene regulation is not understood. Here, we demonstrate an important role for Mcm1p-mediated DNA bending in determining local promoter architecture and permitting the formation of ternary transcription factor complexes. We constructed mutant mcm1 alleles that are defective in protein-induced bending. Defects in nuclear division, cell growth or viability, transcription, and gene expression were observed in these mutants. We identified one likely cause of the cell growth defects as the aberrant formation of the cell cycle-regulatory Fkh2p-Mcm1p complex. Microarray analysis confirmed the importance of Mcm1p-mediated DNA bending in maintaining correct gene expression profiles and revealed defects in Mcm1p-mediated repression of Ty elements and in the expression of the cell cycle-regulated YFR and CHS1 genes. Thus, we discovered an important role for DNA bending by MADS-box proteins in the formation and function of eukaryotic transcription factor complexes.

Present address: Syngenta, CTL, Alderley Park, Macclesfield, Cheshire SK10 4TJ, United Kingdom.

Present address: Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0540.

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