Cross-family transcription factor interaction between MYC2 and GBFs modulates terpenoid indole alkaloid biosynthesis

Xueyi Sui, Sanjay Kumar Singh, Barunava Patra, Craig Schluttenhofer, Wen Guo, Sitakanta Pattanaik, Ling Yuan

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Biosynthesis of medicinally valuable terpenoid indole alkaloids (TIAs) in Catharanthus roseus is regulated by transcriptional activators such as the basic helix-loop-helix factor CrMYC2. However, the transactivation effects are often buffered by repressors, such as the bZIP factors CrGBF1 and CrGBF2, possibly to fine-tune the accumulation of cytotoxic TIAs. Questions remain as to whether and how these factors interact to modulate TIA production. We demonstrated that overexpression of CrMYC2 induces CrGBF expression and results in reduced alkaloid accumulation in C. roseus hairy roots. We found that CrGBF1 and CrGBF2 form homo- and heterodimers to repress the transcriptional activities of key TIA pathway gene promoters. We showed that CrGBFs dimerize with CrMYC2, and CrGBF1 binds to the same cis-elements (T/G-box) as CrMYC2 in the target gene promoters. Our findings suggest that CrGBFs antagonize CrMYC2 transactivation possibly by competitive binding to the T/G-box in the target promoters and/or protein-protein interaction that forms a non-DNA binding complex that prevents CrMYC2 from binding to its target promoters. Homo- and heterodimer formation allows fine-tuning of the amplitude of TIA gene expression. Our findings reveal a previously undescribed regulatory mechanism that governs the TIA pathway genes to balance metabolic flux for TIA production in C. roseus.

Original languageEnglish
Pages (from-to)4267-4281
Number of pages15
JournalJournal of Experimental Botany
Issue number18
StatePublished - Aug 14 2018

Bibliographical note

Funding Information:
We express our gratitude to Drs A. Hunt, G. Hao, and M. Chakrabarti (Department of Plant and Soil Sciences, University of Kentucky) for assistance in RNA-seq library preparation. We thank Mr J. May (Department of Civil Engineering and Environmental Research Training Laboratories, University of Kentucky) for assistance in LC-MS/MS. This research was supported by a graduate scholarship to XS from the Department of Plant and Soil Sciences, University of Kentucky.This work is supported partially by the Harold R. Burton Endowed Professorship to LY and by the National Science Foundation under Cooperative Agreement no. 1355438 to LY.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Experimental Biology.


  • Catharanthus roseus (Madagascar periwinkle)
  • CrGBF1/2
  • CrMYC2
  • Protein-protein interaction
  • Terpenoid indole (vinca) alkaloids
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Plant Science


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