Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 389, Issue 3, Pages 606-618Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2009.04.056
Keywords
DNA binding; Tbx proteins; transcription factor; T-box; T-site
Categories
Funding
- Australian Government
- National Health and Medical Research Counsel (NHMRC) [256302, 354400]
- NHMRC RD Wright Career Development Fellowship
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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 similar to 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. (C) 2009 Elsevier Ltd. All rights reserved.
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