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Cited by 67Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationNeurobiology and Insect Physiology Research

A transcription factor collective defines the HSN serotonergic neuron regulatory landscape

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Lloret-Fernández, Carla, Maicas, Miren, Mora-Martínez, Carlos, Artacho, Alejandro, Jimeno-Martín, Ángela, Chirivella, Laura, Weinberg, Peter, Flames, Nuria·2018·eLife
DOI 10.7554/elife.32785PMC PMC5916565
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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.

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  • Transcription factors governing serotonergic neuron differentiation showed synergy despite flexible sequence organisation of their cognate enhancers.

    “Similarly, TFs governing serotonergic neuron differentiation showed synergy despite flexible sequence organisation of their cognate enhancers [95].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [95]

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Cited by

Sorted by citations

Authors
Lloret-Fernández, C., Maicas, M., Mora-Martínez, C., Artacho, A., Jimeno-Martín, Á., Chirivella, L., Weinberg, P., & Flames, N.
Affiliations
  • Instituto de Biomedicina de Valencia (ES)
  • Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC, Valencia, Spain
  • Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (ES)
  • Howard Hughes Medical Institute (US)
Corresponding author
Flames, Nuria
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-03-22
Volume
7
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.32785
PMC
PMC5916565
OpenAlex
W2789282125
Cited by
67
References
5
Citations by year
2026: 7 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 18 · 2020: 12 · 2019: 5 · 2018: 3
FWCI
3.38
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Columbia Academic Commons (Columbia University)
Funders
  • Ministerio de Economía y Competitividad (SAF2014-56877-R)
  • European Research Council (ERC Stg 2011-281920)
  • Generalitat Valenciana (ACIF/2013/087, ACIF/2015/398)
  • Ministerio de Educación, Cultura y Deporte (FPU14/02651)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
transcription factors, serotonergic neurons, Caenorhabditis elegans, enhancer identification, cell differentiation, deep homology, mouse orthologs, neuronal transcriptome
MeSH terms
Animals, Cell Differentiation, Humans, Mice, Inbred C57BL, Phylogeny, Transcription Factors, Caenorhabditis elegans, Gene Expression Profiling, Caenorhabditis elegans Proteins, Animals, Genetically Modified, HEK293 Cells, Serotonergic Neurons

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