 | Figure 2
Nature Genetics
28, 276 - 280 (2001)
doi:10.1038/90123
Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiationYukio Hiroi, Sumiyo Kudoh, Koshiro Monzen, Yuichi Ikeda, Yoshio Yazaki, Ryozo Nagai
& Issei Komuro | | | | Figure 2. Transactivation of Nppa by Tbx5 and Nkx2-5.
a, Dose-dependent transactivation of Nppa by Tbx5. Co-transfection of Tbx5 expression plasmid and Nppa driving expression of a -2.6 kb promoter luciferase gene shows that overexpression of Tbx5 transactivates the Nppa promoter in a dose-dependent manner. Data represent luciferase activities relative to an internal control. b, Synergistic activation of Nppa by Tbx5 and Nkx2-5. Expression of Tbx5 (50 ng/three dishes) or Nkx2-5 (50 ng/three dishes) results in show only weak transactivation of Nppa, whereas overexpression of both Tbx5 and Nkx2-5 strongly activate Nppa. Neither Xenopus T (brachyury; Bra) nor Hoxb6 transactivates Nppa. There are no synergistic effects between T (brachyury) and Nkx2-5 or Tbx5 and Hoxb6. c, Transactivation of Nppa by deletion mutants of Tbx5 (50 ng/three dishes) with or without Nkx2-5 (50 ng/three dishes). Deletion of the C-terminal domain of Tbx5 ( C) activates Nppa less than full-length Tbx5 does, and it lacks the synergistic effect with Nkx2-5. Deletion of the N-terminal domain of Tbx5 (N) abolishes its transcription of Nppa. d, Transactivation by Tbx5 of Nppa promoters with deletions. Deletion up to -270bp of the Nppa promoter has marginal effects on the transactivation by Tbx5, whereas activation of the promoter containing less than 240bp by Tbx5 is significantly reduced. e, Transactivation and synergistic activation of Nppa by misssense mutants of Tbx5 (50 ng/three dishes). The R237Q mutant, which causes minor cardiac defects in HOS, activates Nppa and shows synergistic activity with Nkx2-5, whereas the G80R mutant that causes severe cardiac malformations activates Nppa significantly less than wildtype Tbx5.
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