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A transcription factor collective defines the HSN serotonergic neuron regulatory landscape

AuthorsLloret-Fernández, Carla; Maicas, Miren; Mora-Martínez, Carlos; Artacho, Alejandro; Jimeno-Martín, Ángela; Chirivella, Laura; Weinberg, Peter; Flames, Nuria
KeywordsC. elegans
cis-regulatory logic
Developmental biology
Neuronal differentiation
Serotonergic neurons
Stem cells
Transcription factors
Issue Date22-Mar-2018
PublishereLife Sciences Publications
CitationeLife 7: e32785 (2018)
AbstractCell 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.
Description36 Pages, 8 Figures, 2 Tables
Publisher version (URL)http://dx.doi.org/10.7554/eLife.32785
Appears in Collections:(IBV) Artículos
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