Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation
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{"title"=>"Differential deployment of REST and CoREST promotes glial subtype specification and oligodendrocyte lineage maturation", "type"=>"journal", "authors"=>[{"first_name"=>"Joseph J.", "last_name"=>"Abrajano", "scopus_author_id"=>"6505889626"}, {"first_name"=>"Irfan A.", "last_name"=>"Qureshi", "scopus_author_id"=>"35119361600"}, {"first_name"=>"Solen", "last_name"=>"Gokhan", "scopus_author_id"=>"6602399465"}, {"first_name"=>"Deyou", "last_name"=>"Zheng", "scopus_author_id"=>"7202567035"}, {"first_name"=>"Aviv", "last_name"=>"Bergman", "scopus_author_id"=>"7201460417"}, {"first_name"=>"Mark F.", "last_name"=>"Mehler", "scopus_author_id"=>"55412568800"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"355633772", "doi"=>"10.1371/journal.pone.0007665", "sgr"=>"70449578270", "scopus"=>"2-s2.0-70449578270", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"19888342"}, "id"=>"af133f4a-427a-34b9-acad-bf7cd25abd3f", "abstract"=>"BACKGROUND: The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.\\n\\nCONCLUSIONS/SIGNIFICANCE: Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states.", "link"=>"http://www.mendeley.com/research/differential-deployment-rest-corest-promotes-glial-subtype-specification-oligodendrocyte-lineage-mat", "reader_count"=>72, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>7, "Researcher"=>20, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>3, "Professor"=>5, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>7, "Researcher"=>20, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>3, "Professor"=>5, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>52, "Neuroscience"=>1, "Chemical Engineering"=>1, "Chemistry"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>52}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"South Korea"=>1, "Belgium"=>1, "United States"=>5, "United Kingdom"=>2, "Spain"=>1}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/434928", "https://ndownloader.figshare.com/files/434958", "https://ndownloader.figshare.com/files/434974", "https://ndownloader.figshare.com/files/434993", "https://ndownloader.figshare.com/files/435019", "https://ndownloader.figshare.com/files/435102"], "description"=>"<div><h3>Background</h3><p>The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.</p><h3>Methodology/Principal Findings</h3><p>We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.</p><h3>Conclusions/Significance</h3><p>Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states.</p></div>", "links"=>[], "tags"=>["differential", "deployment", "corest", "promotes", "glial", "subtype", "specification", "oligodendrocyte", "lineage", "maturation"], "article_id"=>145798, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.s001", "https://dx.doi.org/10.1371/journal.pone.0007665.s002", "https://dx.doi.org/10.1371/journal.pone.0007665.s003", "https://dx.doi.org/10.1371/journal.pone.0007665.s004", "https://dx.doi.org/10.1371/journal.pone.0007665.s005", "https://dx.doi.org/10.1371/journal.pone.0007665.s006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Differential_Deployment_of_REST_and_CoREST_Promotes_Glial_Subtype_Specification_and_Oligodendrocyte_Lineage_Maturation/145798", "title"=>"Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-11-03 01:36:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/877482"], "description"=>"<p>(A) Immunofluorescence microscopy of REST and CoREST (TRITC) expression profiles in glial developmental cell types. REST and CoREST are expressed in the nucleus and cytoplasm of all glial cell types, including astrocytes (AS), oligodendrocyte (OL) precursors (OLpre), OL progenitors (OLpro), post-mitotic OLs (pmOL), and mature, myelin expressing OLs (myOLs). Antibodies to specific OL and AS developmental markers (FITC) were used to identify specific stages of glial cell maturation. Scale bars = 50 µm (OLpres-myOLs) and 10 µm (ASs), respectively. (B) Western blot analysis of REST and CoREST expression in glial developmental species. REST and CoREST are ubiquitously expressed in all cell types examined in our developmental paradigm.</p>", "links"=>[], "tags"=>["subcellular", "localization", "corest", "glial"], "article_id"=>547931, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_and_subcellular_localization_of_REST_and_CoREST_in_glial_developmental_species_/547931", "title"=>"Expression and subcellular localization of REST and CoREST in glial developmental species.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-03 02:12:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/877591"], "description"=>"<p>The number of exclusive REST, exclusive CoREST, and REST and CoREST (REST-CoREST) target genes uniquely present in individual glial cell types as identified through chromatin immunoprecipitation on promoter chip (ChIP-chip) experiments. We identified a total of 3,178 REST target genes and 4,060 CoREST target genes. Note the presence of a disproportionately high number of CoREST target genes in OLpres. (B) The percentages of REST, CoREST, or REST-CoREST target genes present in individual glial developmental cell types that contain previously characterized repressor element-1 (RE1) motifs <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007665#pone.0007665-Bruce1\" target=\"_blank\">[20]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007665#pone.0007665-Otto1\" target=\"_blank\">[22]</a>.</p>", "links"=>[], "tags"=>["corest", "genes", "macroglial"], "article_id"=>548048, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Profiles_of_REST_and_CoREST_target_genes_in_macroglial_developmental_cell_types_/548048", "title"=>"Profiles of REST and CoREST target genes in macroglial developmental cell types.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-03 02:14:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/877671"], "description"=>"<p>The distinct and overlapping profiles of REST, CoREST and REST-CoREST target genes present throughout glial lineage elaboration and in neuronal subtypes [cholinergic neurons (CHOLNs), medium spiny projection neurons (MSNs), GABAergic neurons (GABANs), glutamatergic neurons (GLUTNs)]. These observations are highly statistically significant with corresponding p-values<0.0001 (i.e., cumulative probability calculated using hypergeometric testing) for the number of overlapping glial and neuronal genes in each comparison.</p>", "links"=>[], "tags"=>["corest", "profiles", "glial", "neuronal"], "article_id"=>548123, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparative_analysis_of_REST_and_CoREST_target_gene_profiles_in_glial_and_neuronal_subtypes_/548123", "title"=>"Comparative analysis of REST and CoREST target gene profiles in glial and neuronal subtypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-03 02:15:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/877769"], "description"=>"<p>We examined the distinct and overlapping profiles of REST target genes present in OL lineage species during progressive stages of OL lineage maturation (OLpre → OLpro → pmOL → myOL).</p>", "links"=>[], "tags"=>["profiles", "genes", "seminal", "stages", "oligodendrocyte", "lineage"], "article_id"=>548218, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparative_profiles_of_REST_target_genes_present_during_seminal_stages_of_oligodendrocyte_lineage_elaboration_/548218", "title"=>"Comparative profiles of REST target genes present during seminal stages of oligodendrocyte lineage elaboration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-03 02:16:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/877943"], "description"=>"<p>We examined the distinct and overlapping profiles of CoREST target genes present in OL lineage species during progressive stages of OL lineage maturation (OLpre → OLpro → pmOL → myOL).</p>", "links"=>[], "tags"=>["profiles", "corest", "genes", "seminal", "stages", "oligodendrocyte", "lineage"], "article_id"=>548390, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparative_profiles_of_CoREST_target_genes_present_during_seminal_stages_of_oligodendrocyte_lineage_elaboration_/548390", "title"=>"Comparative profiles of CoREST target genes present during seminal stages of oligodendrocyte lineage elaboration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-03 02:19:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/878030"], "description"=>"<p>We examined REST and CoREST target gene expression profiles during the specification of ASs (NSCs→ASs) and OLpres (N/OPs→OLpres) and during progressive stages of OL lineage maturation (OLpres→OLpros, OLpros→ pmOLs, and pmOLs→myOLs). The absence or presence of REST and CoREST promoter occupancy for target genes within each cell type are indicated by no and yes. Each pair of numbers represents genes up regulated and down regulated (+/−), respectively, during the transition from the proximal progenitor (column A) to its immediate progeny (column B).</p>", "links"=>[], "tags"=>["corest", "promoter", "occupancy", "corresponding", "profiles", "glial"], "article_id"=>548478, "categories"=>["Neuroscience"], "users"=>["Joseph J. Abrajano", "Irfan A. Qureshi", "Solen Gokhan", "Deyou Zheng", "Aviv Bergman", "Mark F. Mehler"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007665.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparative_analysis_of_REST_and_CoREST_promoter_occupancy_and_corresponding_gene_expression_profiles_during_glial_developmental_transitions_/548478", "title"=>"Comparative analysis of REST and CoREST promoter occupancy and corresponding gene expression profiles during glial developmental transitions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-03 02:21:18"}

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  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2021", "month"=>"1"}

Relative Metric

{"start_date"=>"2009-01-01T00:00:00Z", "end_date"=>"2009-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[349, 614, 744, 851, 955, 1059, 1167, 1262, 1352, 1431, 1516, 1593, 1668, 1746, 1817, 1883, 1950, 2017, 2075, 2141, 2198, 2254, 2313, 2368, 2424, 2474, 2534, 2591, 2651, 2710, 2776, 2837, 2892, 2953, 3014, 3072, 3130, 3186, 3251, 3307, 3366, 3427, 3500, 3561, 3627, 3688, 3759, 3821, 3888, 3950, 4010, 4070, 4131, 4189, 4242, 4307, 4370, 4431, 4491, 4549, 4608]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[336, 588, 721, 826, 931, 1029, 1138, 1224, 1311, 1395, 1477, 1555, 1632, 1704, 1774, 1847, 1919, 1987, 2039, 2089, 2149, 2204, 2264, 2319, 2370, 2424, 2481, 2535, 2593, 2645, 2702, 2765, 2816, 2865, 2932, 2992, 3045, 3105, 3159, 3208, 3259, 3316, 3374, 3430, 3490, 3542, 3602, 3654, 3720, 3783, 3851, 3919, 3981, 4038, 4096, 4151, 4197, 4235, 4297, 4372, 4437]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[366, 637, 775, 896, 999, 1118, 1230, 1322, 1416, 1516, 1602, 1685, 1767, 1849, 1914, 1982, 2049, 2120, 2185, 2246, 2303, 2363, 2409, 2473, 2535, 2599, 2655, 2717, 2777, 2842, 2906, 2977, 3021, 3088, 3144, 3199, 3253, 3317, 3379, 3456, 3508, 3567, 3634, 3716, 3781, 3853, 3911, 3974, 4040, 4118, 4170, 4218, 4285, 4341, 4404, 4467, 4527, 4584, 4631, 4689, 4725]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[334, 613, 751, 863, 964, 1078, 1181, 1270, 1358, 1443, 1536, 1616, 1690, 1768, 1826, 1902, 1969, 2031, 2095, 2149, 2202, 2258, 2305, 2349, 2417, 2482, 2541, 2598, 2662, 2720, 2768, 2832, 2897, 2947, 2998, 3058, 3121, 3175, 3235, 3292, 3368, 3442, 3507, 3563, 3621, 3676, 3736, 3802, 3852, 3922, 3977, 4025, 4071, 4141, 4199, 4258, 4316, 4376, 4422, 4467, 4518]}]}
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