PT  - JOURNAL ARTICLE
AU  - Chaogu Zheng
AU  - Felix Qiaochu Jin
AU  - Brian Loeber Trippe
AU  - Martin Chalfie
TI  - ZAG-1/ZEB and EGL-44/TEAD form a negative feedback loop to safeguard the choice of cell fate
AID  - 10.1101/320978
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 320978
4099  - http://biorxiv.org/content/early/2018/05/11/320978.short
4100  - http://biorxiv.org/content/early/2018/05/11/320978.full
AB  - Terminal differentiation generates the specialized structures and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called “terminal selectors” that directly activate a set of effector genes. Using the mechanosensory touch receptor neurons (TRNs) in Caenorhabditis elegans, we extend this concept by identifying non-selector regulators of cell fate, which promote TRN fate indirectly by safeguarding the stability and activity of the selectors. In particular, the ZEB family transcriptional repressor ZAG-1 promotes TRN fate by inhibiting the TEA domain transcription factor EGL-44 and its binding partner EGL-46. EGL-44 and EGL-46 inhibit the TRN fate and simultaneously induce the fate of the multidendritic nociceptor FLP neurons. Since TRN and FLP share the same terminal selectors and a common ground state, the mutual inhibition between ZAG-1 and EGL-44 forms a negative feedback loop to regulate the choice between the two neuronal fates.