REST and Its Corepressors Mediate Plasticity of Neuronal Gene Chromatin throughout Neurogenesis

Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just suff...

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Published in	Cell Vol. 121; no. 4; pp. 645 - 657
Main Authors	Ballas, Nurit, Grunseich, Christopher, Lu, Diane D., Speh, Joan C., Mandel, Gail
Format	Journal Article
Language	English
Published	United States Elsevier Inc 20.05.2005
Subjects	Animals Cell Differentiation - genetics Cells, Cultured Chromatin - genetics Chromatin - metabolism DNA Methylation DNA-Binding Proteins - metabolism Gene Expression Regulation, Developmental - genetics Genes, Regulator - genetics Mice Nerve Tissue Proteins - metabolism Nervous System - embryology Neuronal Plasticity - genetics Neurons - metabolism Pluripotent Stem Cells - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism Transcription Factors - genetics Transcription Factors - metabolism
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Abstract	Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its corepressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.
AbstractList	Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its co-repressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its co-repressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli. Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its corepressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli. Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its co-repressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.
Author	Mandel, Gail Speh, Joan C. Ballas, Nurit Lu, Diane D. Grunseich, Christopher
Author_xml	– sequence: 1 givenname: Nurit surname: Ballas fullname: Ballas, Nurit email: nballas@notes.cc.sunysb.edu – sequence: 2 givenname: Christopher surname: Grunseich fullname: Grunseich, Christopher – sequence: 3 givenname: Diane D. surname: Lu fullname: Lu, Diane D. – sequence: 4 givenname: Joan C. surname: Speh fullname: Speh, Joan C. – sequence: 5 givenname: Gail surname: Mandel fullname: Mandel, Gail
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/15907476$$D View this record in MEDLINE/PubMed
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Snippet	Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to...
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SubjectTerms	Animals Cell Differentiation - genetics Cells, Cultured Chromatin - genetics Chromatin - metabolism DNA Methylation DNA-Binding Proteins - metabolism Gene Expression Regulation, Developmental - genetics Genes, Regulator - genetics Mice Nerve Tissue Proteins - metabolism Nervous System - embryology Neuronal Plasticity - genetics Neurons - metabolism Pluripotent Stem Cells - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism Transcription Factors - genetics Transcription Factors - metabolism
Title	REST and Its Corepressors Mediate Plasticity of Neuronal Gene Chromatin throughout Neurogenesis
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