703 / 2019-05-02 00:11:19

The interplay between transcription factor levels, stability and transcriptional switch: Data-driven multiscale models of stem cell homeostasis

Arabidopsis, shoot meristem, stem cells, development

Growth and Development > Growth and Development

The regulation and interpretation of transcription factor levels are critical in the spatiotemporal control of gene expression. WUSCHEL, a stem cell-promoting transcription factor activates and represses transcription at lower and higher levels respectively. The differential accumulation of WUSCHEL in adjacent cells is critical for spatial regulation and the level of CLAVATA3, a negative regulator of WUSCHEL transcription, to establish the overall gradient. The subcellular partitioning controls the WUSCHEL protein level, stability, and spatial distribution. We provide evidence that CLV3 signaling acts post-translationally in shaping the WUS gradient along with the cytokinin signaling. We develop a 3D cell-based mathematical model which integrates sub-cellular partitioning with a cellular concentration across the spatial domain to analyze the regulation of WUS. By using this model, we investigate the mechanisms of the maintenance of the WUS gradient within the tissue. In parallel, we developed a hybrid ODE mathematical model of stochastic binding and unbinding of WUS to cis-elements regulating CLV3 expression and integrated with the deterministic dynamics that account for WUS protein dynamics. By using the hybrid model, we have explored hypotheses regarding the nature of co-operative interactions among cis-elements, the influence of WUS complex stoichiometry on the transcriptional switching behavior and the CLV3 signaling feedback on the regulation of WUS protein levels.