Cargando…

Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans

Although epigenetic control of stem cell fate choice is well established, little is known about epigenetic regulation of terminal neuronal differentiation. We found that some differences among the subtypes of Caenorhabditis elegans VC neurons, particularly the expression of the transcription factor...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Chaogu, Karimzadegan, Siavash, Chiang, Victor, Chalfie, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861114/
https://www.ncbi.nlm.nih.gov/pubmed/24348272
http://dx.doi.org/10.1371/journal.pgen.1004017
_version_ 1782295596499992576
author Zheng, Chaogu
Karimzadegan, Siavash
Chiang, Victor
Chalfie, Martin
author_facet Zheng, Chaogu
Karimzadegan, Siavash
Chiang, Victor
Chalfie, Martin
author_sort Zheng, Chaogu
collection PubMed
description Although epigenetic control of stem cell fate choice is well established, little is known about epigenetic regulation of terminal neuronal differentiation. We found that some differences among the subtypes of Caenorhabditis elegans VC neurons, particularly the expression of the transcription factor gene unc-4, require histone modification, most likely H3K9 methylation. An EGF signal from the vulva alleviated the epigenetic repression of unc-4 in vulval VC neurons but not the more distant nonvulval VC cells, which kept unc-4 silenced. Loss of the H3K9 methyltransferase MET-2 or H3K9me2/3 binding proteins HPL-2 and LIN-61 or a novel chromodomain protein CEC-3 caused ectopic unc-4 expression in all VC neurons. Downstream of the EGF signaling in vulval VC neurons, the transcription factor LIN-11 and histone demethylases removed the suppressive histone marks and derepressed unc-4. Behaviorally, expression of UNC-4 in all the VC neurons caused an imbalance in the egg-laying circuit. Thus, epigenetic mechanisms help establish subtype-specific gene expression, which are needed for optimal activity of a neural circuit.
format Online
Article
Text
id pubmed-3861114
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38611142013-12-17 Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans Zheng, Chaogu Karimzadegan, Siavash Chiang, Victor Chalfie, Martin PLoS Genet Research Article Although epigenetic control of stem cell fate choice is well established, little is known about epigenetic regulation of terminal neuronal differentiation. We found that some differences among the subtypes of Caenorhabditis elegans VC neurons, particularly the expression of the transcription factor gene unc-4, require histone modification, most likely H3K9 methylation. An EGF signal from the vulva alleviated the epigenetic repression of unc-4 in vulval VC neurons but not the more distant nonvulval VC cells, which kept unc-4 silenced. Loss of the H3K9 methyltransferase MET-2 or H3K9me2/3 binding proteins HPL-2 and LIN-61 or a novel chromodomain protein CEC-3 caused ectopic unc-4 expression in all VC neurons. Downstream of the EGF signaling in vulval VC neurons, the transcription factor LIN-11 and histone demethylases removed the suppressive histone marks and derepressed unc-4. Behaviorally, expression of UNC-4 in all the VC neurons caused an imbalance in the egg-laying circuit. Thus, epigenetic mechanisms help establish subtype-specific gene expression, which are needed for optimal activity of a neural circuit. Public Library of Science 2013-12-12 /pmc/articles/PMC3861114/ /pubmed/24348272 http://dx.doi.org/10.1371/journal.pgen.1004017 Text en © 2013 Zheng et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zheng, Chaogu
Karimzadegan, Siavash
Chiang, Victor
Chalfie, Martin
Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
title Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
title_full Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
title_fullStr Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
title_full_unstemmed Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
title_short Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans
title_sort histone methylation restrains the expression of subtype-specific genes during terminal neuronal differentiation in caenorhabditis elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861114/
https://www.ncbi.nlm.nih.gov/pubmed/24348272
http://dx.doi.org/10.1371/journal.pgen.1004017
work_keys_str_mv AT zhengchaogu histonemethylationrestrainstheexpressionofsubtypespecificgenesduringterminalneuronaldifferentiationincaenorhabditiselegans
AT karimzadegansiavash histonemethylationrestrainstheexpressionofsubtypespecificgenesduringterminalneuronaldifferentiationincaenorhabditiselegans
AT chiangvictor histonemethylationrestrainstheexpressionofsubtypespecificgenesduringterminalneuronaldifferentiationincaenorhabditiselegans
AT chalfiemartin histonemethylationrestrainstheexpressionofsubtypespecificgenesduringterminalneuronaldifferentiationincaenorhabditiselegans