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J Mol Biol. 2009 Jun 12;389(3):606-18. doi: 10.1016/j.jmb.2009.04.056. Epub 2009 May 3.

Conformational stability and DNA binding specificity of the cardiac T-box transcription factor Tbx20.

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School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW 2006, Australia.


The transcription factor Tbx20 acts within a hierarchy of T-box factors in lineage specification and morphogenesis in the mammalian heart and is mutated in congenital heart disease. T-box family members share a approximately 20-kDa DNA-binding domain termed the T-box. The question of how highly homologous T-box proteins achieve differential transcriptional control in heart development, while apparently binding to the same DNA sequence, remains unresolved. Here we show that the optimal DNA recognition sequence for the T-box of Tbx20 corresponds to a T-half-site. Furthermore, we demonstrate using purified recombinant domains that distinct T-boxes show significant differences in the affinity and kinetics of binding and in conformational stability, with the T-box of Tbx20 displaying molten globule character. Our data highlight unique features of Tbx20 and suggest mechanistic ways in which cardiac T-box factors might interact synergistically and/or competitively within the cardiac regulatory network.

[Indexed for MEDLINE]

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