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A transcription factor collective defines the HSN serotonergic neuron regulatory landscape

Lloret-Fernandez, C; Maicas, M; Mora-Martinez, C; Artacho, A; Jimeno-Martin, A; Chirivella, L; Weinberg, P; (2018) A transcription factor collective defines the HSN serotonergic neuron regulatory landscape. eLife , 7 , Article e32785. 10.7554/elife.32785. Green open access

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Abstract

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.

Type: Article
Title: A transcription factor collective defines the HSN serotonergic neuron regulatory landscape
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/elife.32785
Publisher version: https://doi.org/10.7554/eLife.32785.001
Language: English
Additional information: © 2018, Lloret-Fernández et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10073893
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