PT  - JOURNAL ARTICLE
AU  - Angela Jimeno-Martín
AU  - Erick Sousa
AU  - Noemi Daroqui
AU  - Rebeca Brocal-Ruiz
AU  - Miren Maicas
AU  - Nuria Flames
TI  - Transcription factors from multiple families ensure enhancer selectivity and robust neuron terminal differentiation
AID  - 10.1101/2020.09.04.283036
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.04.283036
4099  - http://biorxiv.org/content/early/2020/09/04/2020.09.04.283036.short
4100  - http://biorxiv.org/content/early/2020/09/04/2020.09.04.283036.full
AB  - To search for general principles underlying neuronal regulatory programs we built an RNA interference library against all transcription factors (TFs) encoded in C. elegans genome and systematically screened for specification defects in ten different neuron types of the monoaminergic (MA) superclass.We identified over 90 TFs involved in MA specification, with at least ten different TFs controlling differentiation of each individual neuron type. These TFs belong predominantly to five TF families (HD, bHLH, ZF, bZIP and NHR). Next, focusing on the complexity of terminal differentiation, we identified and functionally characterized the dopaminergic terminal regulatory program. We found that seven TFs from four different families act in a TF collective to provide genetic robustness and to impose a specific gene regulatory signature enriched in the regulatory regions of dopamine effector genes. Our results provide new insights on neuron-type regulatory programs that could help better understand specification and evolution of neuron types.Competing Interest StatementThe authors have declared no competing interest.