1. A transcription factor collective defines the HSN serotonergic neuron regulatory landscape
- Author
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Alejandro Artacho, Miren Maicas, Peter Weinberg, Carlos Mora-Martínez, Angela Jimeno-Martin, Laura Chirivella, Nuria Flames, Carla Lloret-Fernandez, Ministerio de Economía y Competitividad (España), European Research Council, Ministerio de Educación, Cultura y Deporte (España), Flames, Nuria, and Flames, Nuria [0000-0003-0961-0609]
- Subjects
0301 basic medicine ,Mouse ,Cellular differentiation ,Stem cells ,Transcriptome ,Animals, Genetically Modified ,Serotonergic neurons ,Developmental neurobiology ,Biology (General) ,Caenorhabditis elegans ,Phylogeny ,Neurons ,General Neuroscience ,Cell Differentiation ,General Medicine ,serotonergic neurons ,medicine.anatomical_structure ,Neuronal differentiation ,C. elegans ,Medicine ,Research Article ,Serotonin ,QH301-705.5 ,Science ,Biology ,Serotonergic ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,transcription factors ,Developmental biology ,medicine ,Transcription factors ,Animals ,Humans ,Enhancer ,Caenorhabditis elegans Proteins ,Transcription factor ,neuronal differentiation ,cis-regulatory logic ,General Immunology and Microbiology ,FOS: Clinical medicine ,Gene Expression Profiling ,Neurosciences ,biology.organism_classification ,Mice, Inbred C57BL ,030104 developmental biology ,Developmental Biology and Stem Cells ,HEK293 Cells ,Neuron ,Neuroscience - Abstract
36 Pages, 8 Figures, 2 Tables, 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., Ministerio de Economáa y Competitividad SAF2014-56877-R. European Research Council ERC Stg 2011-281920. Generalitat Valenciana ACIF/2013/087. Ministerio de Educación, Cultura y Deporte FPU14/02651. Generalitat Valenciana ACIF/2015/398
- Published
- 2018