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A transcription factor collective defines the HSN serotonergic neuron regulatory landscape

AutorLloret-Fernández, Carla; Maicas, Miren; Mora-Martínez, Carlos; Artacho, Alejandro; Jimeno-Martín, Ángela; Chirivella, Laura; Weinberg, Peter; Flames, Nuria
Palabras claveC. elegans
cis-regulatory logic
Developmental biology
Mouse
Neuronal differentiation
Neuroscience
Serotonergic neurons
Stem cells
Transcription factors
Fecha de publicación22-mar-2018
EditoreLife Sciences Publications
CitacióneLife 7: e32785 (2018)
ResumenCell 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.
Descripción36 Pages, 8 Figures, 2 Tables
Versión del editorhttp://dx.doi.org/10.7554/eLife.32785
URIhttp://hdl.handle.net/10261/166313
DOI10.7554/eLife.32785
E-ISSN2050-084X
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