TY - JOUR TI - A transcription factor collective defines the HSN serotonergic neuron regulatory landscape AU - Lloret-Fernández, Carla AU - Maicas, Miren AU - Mora-Martínez, Carlos AU - Artacho, Alejandro AU - Jimeno-Martín, Ángela AU - Chirivella, Laura AU - Weinberg, Peter AU - Flames, Nuria A2 - Sengupta, Piali VL - 7 PY - 2018 DA - 2018/03/19 SP - e32785 C1 - eLife 2018;7:e32785 DO - 10.7554/eLife.32785 UR - https://doi.org/10.7554/eLife.32785 AB - Cell differentiation is controlled by individual transcription factors (TFs) that together activate a selection of enhancers in specific cell types. How these combinations of TFs identify and activate their target sequences remains poorly understood. Here, we identify the cis-regulatory transcriptional code that controls the differentiation of serotonergic HSN neurons in Caenorhabditis elegans. Activation of the HSN transcriptome is directly orchestrated by a collective of six TFs. Binding site clusters for this TF collective form a regulatory signature that is sufficient for de novo identification of HSN neuron functional enhancers. Among C. elegans neurons, the HSN transcriptome most closely resembles that of mouse serotonergic neurons. Mouse orthologs of the HSN TF collective also regulate serotonergic differentiation and can functionally substitute for their worm counterparts which suggests deep homology. Our results identify rules governing the regulatory landscape of a critically important neuronal type in two species separated by over 700 million years. KW - neuronal differentiation KW - cis-regulatory logic KW - transcription factors KW - serotonergic neurons JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -