A Transcription Factor Collective Defines the HSN Serotonergic Neuron Regulatory Landscape

Overview

Journal Elife

Specialty Biology

Date 2018 Mar 20

PMID 29553368

Citations 34

Authors

Carla Lloret-Fernandez

Miren Maicas

Carlos Mora-Martinez

Alejandro Artacho

Angela Jimeno-Martin

Laura Chirivella

Peter Weinberg

Nuria Flames

Affiliations

Soon will be listed here.

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 -regulatory transcriptional code that controls the differentiation of serotonergic HSN neurons in . 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 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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References

Gerstein M, Lu Z, Van Nostrand E, Cheng C, Arshinoff B, Liu T . Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science. 2010; 330(6012):1775-87. PMC: 3142569. DOI: 10.1126/science.1196914. View

Hobert O . Terminal Selectors of Neuronal Identity. Curr Top Dev Biol. 2016; 116:455-75. DOI: 10.1016/bs.ctdb.2015.12.007. View

Breslin M, Zhu M, Notkins A, Lan M . Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence. Nucleic Acids Res. 2002; 30(4):1038-45. PMC: 100352. DOI: 10.1093/nar/30.4.1038. View

Sommer L, Shah N, Rao M, Anderson D . The cellular function of MASH1 in autonomic neurogenesis. Neuron. 1995; 15(6):1245-58. DOI: 10.1016/0896-6273(95)90005-5. View

Mo A, Mukamel E, Davis F, Luo C, Henry G, Picard S . Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. Neuron. 2015; 86(6):1369-84. PMC: 4499463. DOI: 10.1016/j.neuron.2015.05.018. View

Jacob J, Storm R, Castro D, Milton C, Pla P, Guillemot F . Insm1 (IA-1) is an essential component of the regulatory network that specifies monoaminergic neuronal phenotypes in the vertebrate hindbrain. Development. 2009; 136(14):2477-85. PMC: 2729354. DOI: 10.1242/dev.034546. View

Whitfield T, Wang J, Collins P, Partridge E, Force Aldred S, Trinklein N . Functional analysis of transcription factor binding sites in human promoters. Genome Biol. 2012; 13(9):R50. PMC: 3491394. DOI: 10.1186/gb-2012-13-9-r50. View

Doonan R, Hatzold J, Raut S, Conradt B, Alfonso A . HLH-3 is a C. elegans Achaete/Scute protein required for differentiation of the hermaphrodite-specific motor neurons. Mech Dev. 2008; 125(9-10):883-93. DOI: 10.1016/j.mod.2008.06.002. View

Shimodaira H . An approximately unbiased test of phylogenetic tree selection. Syst Biol. 2002; 51(3):492-508. DOI: 10.1080/10635150290069913. View

10.

Xu Z, Jiang H, Zhong P, Yan Z, Chen S, Feng J . Direct conversion of human fibroblasts to induced serotonergic neurons. Mol Psychiatry. 2015; 21(1):62-70. PMC: 4518549. DOI: 10.1038/mp.2015.101. View

11.

Koh K, Peyrot S, Wood C, Wagmaister J, Maduro M, Eisenmann D . Cell fates and fusion in the C. elegans vulval primordium are regulated by the EGL-18 and ELT-6 GATA factors -- apparent direct targets of the LIN-39 Hox protein. Development. 2002; 129(22):5171-80. DOI: 10.1242/dev.129.22.5171. View

12.

Wapinski O, Vierbuchen T, Qu K, Lee Q, Chanda S, Fuentes D . Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell. 2013; 155(3):621-35. PMC: 3871197. DOI: 10.1016/j.cell.2013.09.028. View

13.

Stefanakis N, Carrera I, Hobert O . Regulatory Logic of Pan-Neuronal Gene Expression in C. elegans. Neuron. 2015; 87(4):733-50. PMC: 4545498. DOI: 10.1016/j.neuron.2015.07.031. View

14.

Basson M, Horvitz H . The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein. Genes Dev. 1996; 10(15):1953-65. DOI: 10.1101/gad.10.15.1953. View

15.

Wyler S, Spencer W, Green N, Rood B, Crawford L, Craige C . Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability. J Neurosci. 2016; 36(5):1758-74. PMC: 4737783. DOI: 10.1523/JNEUROSCI.3798-15.2016. View

16.

Andersen J, Urban N, Achimastou A, Ito A, Simic M, Ullom K . A transcriptional mechanism integrating inputs from extracellular signals to activate hippocampal stem cells. Neuron. 2014; 83(5):1085-97. PMC: 4157576. DOI: 10.1016/j.neuron.2014.08.004. View

17.

Zhang F, Bhattacharya A, Nelson J, Abe N, Gordon P, Lloret-Fernandez C . The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types. Development. 2013; 141(2):422-35. PMC: 3879818. DOI: 10.1242/dev.099721. View

18.

Luo S, Horvitz H . The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage. Curr Biol. 2017; 27(5):661-672. PMC: 5384724. DOI: 10.1016/j.cub.2017.01.056. View

19.

Castro D, Martynoga B, Parras C, Ramesh V, Pacary E, Johnston C . A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets. Genes Dev. 2011; 25(9):930-45. PMC: 3084027. DOI: 10.1101/gad.627811. View

20.

Merika M, Orkin S . DNA-binding specificity of GATA family transcription factors. Mol Cell Biol. 1993; 13(7):3999-4010. PMC: 359949. DOI: 10.1128/mcb.13.7.3999-4010.1993. View