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Coordinated control of terminal differentiation and restriction of cellular plasticity

The acquisition of a specific cellular identity is usually paralleled by a restriction of cellular plasticity. Whether and how these two processes are coordinated is poorly understood. Transcription factors called terminal selectors activate identity-specific effector genes during neuronal different...

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Detalles Bibliográficos
Autores principales: Patel, Tulsi, Hobert, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397285/
https://www.ncbi.nlm.nih.gov/pubmed/28422646
http://dx.doi.org/10.7554/eLife.24100
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author Patel, Tulsi
Hobert, Oliver
author_facet Patel, Tulsi
Hobert, Oliver
author_sort Patel, Tulsi
collection PubMed
description The acquisition of a specific cellular identity is usually paralleled by a restriction of cellular plasticity. Whether and how these two processes are coordinated is poorly understood. Transcription factors called terminal selectors activate identity-specific effector genes during neuronal differentiation to define the structural and functional properties of a neuron. To study restriction of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE-1 results in activation of ASE neuron type-specific effector genes. Once cells differentiate, their plasticity is restricted and ectopic expression of CHE-1 no longer results in activation of ASE effector genes. In striking contrast, removal of the respective terminal selectors of other sensory, inter-, or motor neuron types now enables ectopically expressed CHE-1 to activate its ASE-specific effector genes, indicating that terminal selectors not only activate effector gene batteries but also control the restriction of cellular plasticity. Terminal selectors mediate this restriction at least partially by organizing chromatin. The chromatin structure of a CHE-1 target locus is less compact in neurons that lack their resident terminal selector and genetic epistasis studies with H3K9 methyltransferases suggest that this chromatin modification acts downstream of a terminal selector to restrict plasticity. Taken together, terminal selectors activate identity-specific genes and make non-identity-defining genes less accessible, thereby serving as a checkpoint to coordinate identity specification with restriction of cellular plasticity. DOI: http://dx.doi.org/10.7554/eLife.24100.001
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spelling pubmed-53972852017-04-20 Coordinated control of terminal differentiation and restriction of cellular plasticity Patel, Tulsi Hobert, Oliver eLife Neuroscience The acquisition of a specific cellular identity is usually paralleled by a restriction of cellular plasticity. Whether and how these two processes are coordinated is poorly understood. Transcription factors called terminal selectors activate identity-specific effector genes during neuronal differentiation to define the structural and functional properties of a neuron. To study restriction of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE-1 results in activation of ASE neuron type-specific effector genes. Once cells differentiate, their plasticity is restricted and ectopic expression of CHE-1 no longer results in activation of ASE effector genes. In striking contrast, removal of the respective terminal selectors of other sensory, inter-, or motor neuron types now enables ectopically expressed CHE-1 to activate its ASE-specific effector genes, indicating that terminal selectors not only activate effector gene batteries but also control the restriction of cellular plasticity. Terminal selectors mediate this restriction at least partially by organizing chromatin. The chromatin structure of a CHE-1 target locus is less compact in neurons that lack their resident terminal selector and genetic epistasis studies with H3K9 methyltransferases suggest that this chromatin modification acts downstream of a terminal selector to restrict plasticity. Taken together, terminal selectors activate identity-specific genes and make non-identity-defining genes less accessible, thereby serving as a checkpoint to coordinate identity specification with restriction of cellular plasticity. DOI: http://dx.doi.org/10.7554/eLife.24100.001 eLife Sciences Publications, Ltd 2017-04-19 /pmc/articles/PMC5397285/ /pubmed/28422646 http://dx.doi.org/10.7554/eLife.24100 Text en © 2017, Patel et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Patel, Tulsi
Hobert, Oliver
Coordinated control of terminal differentiation and restriction of cellular plasticity
title Coordinated control of terminal differentiation and restriction of cellular plasticity
title_full Coordinated control of terminal differentiation and restriction of cellular plasticity
title_fullStr Coordinated control of terminal differentiation and restriction of cellular plasticity
title_full_unstemmed Coordinated control of terminal differentiation and restriction of cellular plasticity
title_short Coordinated control of terminal differentiation and restriction of cellular plasticity
title_sort coordinated control of terminal differentiation and restriction of cellular plasticity
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397285/
https://www.ncbi.nlm.nih.gov/pubmed/28422646
http://dx.doi.org/10.7554/eLife.24100
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