Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-β Pathway
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{"title"=>"Epigenetics and preeclampsia: Defining functional epimutations in the preeclamptic placenta related to the TGF-β pathway", "type"=>"journal", "authors"=>[{"first_name"=>"Elizabeth", "last_name"=>"Martin", "scopus_author_id"=>"57190950982"}, {"first_name"=>"Paul D.", "last_name"=>"Ray", "scopus_author_id"=>"56711591000"}, {"first_name"=>"Lisa", "last_name"=>"Smeester", "scopus_author_id"=>"8847468000"}, {"first_name"=>"Matthew R.", "last_name"=>"Grace", "scopus_author_id"=>"57004391000"}, {"first_name"=>"Kim", "last_name"=>"Boggess", "scopus_author_id"=>"7003669118"}, {"first_name"=>"Rebecca C.", "last_name"=>"Fry", "scopus_author_id"=>"8044629400"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84949937612", "pmid"=>"26510177", "sgr"=>"84949937612", "doi"=>"10.1371/journal.pone.0141294", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"607232444"}, "id"=>"946d7f60-9484-35b1-8594-e13272fcd232", "abstract"=>"Preeclampsia is a potentially fatal pregnancy disorder affecting millions of women around the globe. Dysregulation in gene and protein expression within key biological pathways controlling angiogenesis has been implicated in the development of preeclampsia. Altered CpG methylation, a type of epimutation, may underlie this pathway dysregulation. In the present study, placental tissue from preeclamptic cases and normotensive controls was analyzed for genome-wide differential CpG methylation and concomitant changes in gene expression. A set of 123 genes, representing 19.9% of all genes with altered CpG methylation, was associated with functional changes in transcript levels. Underscoring the complex relationships between CpG methylation and gene expression, here hypermethylation was never associated with gene silencing, nor was hypomethylation always associated with gene activation. Moreover, the genomic region of the CpG mark was important in predicting the relationship between CpG methylation and gene expression. The 123 genes were enriched for their involvement in the transforming growth factor beta (TGF-β) signaling pathway, a known regulator of placental trophoblast invasion and migration. This is the first study to identify CpG hypomethylation as an activator of TGF-β-associated gene expression in the preeclamptic placenta. The results suggest functional epimutations are associated with preeclampsia disease status and the identified genes may represent novel biomarkers of disease.", "link"=>"http://www.mendeley.com/research/epigenetics-preeclampsia-defining-functional-epimutations-preeclamptic-placenta-related-tgf%CE%B2-pathway", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>4, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Student > Master"=>2, "Student > Bachelor"=>3, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>4, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Student > Master"=>2, "Student > Bachelor"=>3, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Hungary"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2385655"], "description"=>"<p>Preeclampsia is associated with differential methylation and expression (not shown) of 132 differentially methylated probes (DMPs) representing 123 unique genes (fDMGs). Methylation levels are <i>z</i>-score normalized across rows; red indicates relatively higher levels of methylation and blue indicates relatively lower levels of methylation<b>.</b></p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587765, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.g001", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_heatmap_displays_the_relative_methylation_levels_of_the_132_DMPs_across_subjects_/1587765", "title"=>"The heatmap displays the relative methylation levels of the 132 DMPs across subjects.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385656"], "description"=>"<p>The plots display the three observed relationships of CpG methylation and gene expression. For each plot, the median β value for the preeclamptic and normotensive subjects is provided. The total number of genes (n) identified in the study that display a similar pattern as the representative genes is detailed.</p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587766, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.g002", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plots_of_CpG_methylation_levels_and_gene_expression_levels_across_all_subjects_for_three_representative_genes_/1587766", "title"=>"Plots of CpG methylation levels and gene expression levels across all subjects for three representative genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385658"], "description"=>"<p>The colors represent the different lines of evidence: green represents associations determined by literature searches, magenta represents experimentally-derived evidence, and blue represents associations reported in databases.</p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587768, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.g003", "stats"=>{"downloads"=>4, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_interaction_network_showing_the_relationships_between_differentially_methylated_genes_within_the_TGF_946_pathway_/1587768", "title"=>"Protein interaction network showing the relationships between differentially methylated genes within the TGF-β pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385660"], "description"=>"<p>* p value < .05</p><p>Demographic characteristics of the study subjects.</p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587769, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_characteristics_of_the_study_subjects_/1587769", "title"=>"Demographic characteristics of the study subjects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385661"], "description"=>"<p>Methylation status for differentially methylated probes (DMPs) or functionally- changed differentially methylated probes (fDMPs).</p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587770, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Methylation_status_for_differentially_methylated_probes_DMPs_or_functionally_changed_differentially_methylated_probes_fDMPs_/1587770", "title"=>"Methylation status for differentially methylated probes (DMPs) or functionally- changed differentially methylated probes (fDMPs).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385662"], "description"=>"<p>Hypermethylation (hyper) and hypomethylation (hypo) in relationship to preeclampsia are detailed.</p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587771, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.t003", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_and_percent_of_differentially_methylated_probes_DMPs_or_functionally_changed_differentially_methylated_probes_fDMPs_identified_based_on_genomic_region_/1587771", "title"=>"Number and percent of differentially methylated probes (DMPs) or functionally-changed differentially methylated probes (fDMPs) identified based on genomic region.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385663"], "description"=>"<p>Transcription factors with enriched binding sites among the TGF-β pathway-associated genes.</p>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587772, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141294.t004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transcription_factors_with_enriched_binding_sites_among_the_TGF_946_pathway_associated_genes_/1587772", "title"=>"Transcription factors with enriched binding sites among the TGF-β pathway-associated genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-28 03:26:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2385667", "https://ndownloader.figshare.com/files/2385668", "https://ndownloader.figshare.com/files/2385669", "https://ndownloader.figshare.com/files/2385670", "https://ndownloader.figshare.com/files/2385671", "https://ndownloader.figshare.com/files/2385672"], "description"=>"<div><p>Preeclampsia is a potentially fatal pregnancy disorder affecting millions of women around the globe. Dysregulation in gene and protein expression within key biological pathways controlling angiogenesis has been implicated in the development of preeclampsia. Altered CpG methylation, a type of epimutation, may underlie this pathway dysregulation. In the present study, placental tissue from preeclamptic cases and normotensive controls was analyzed for genome-wide differential CpG methylation and concomitant changes in gene expression. A set of 123 genes, representing 19.9% of all genes with altered CpG methylation, was associated with functional changes in transcript levels. Underscoring the complex relationships between CpG methylation and gene expression, here hypermethylation was never associated with gene silencing, nor was hypomethylation always associated with gene activation. Moreover, the genomic region of the CpG mark was important in predicting the relationship between CpG methylation and gene expression. The 123 genes were enriched for their involvement in the transforming growth factor beta (TGF-β) signaling pathway, a known regulator of placental trophoblast invasion and migration. This is the first study to identify CpG hypomethylation as an activator of TGF-β-associated gene expression in the preeclamptic placenta. The results suggest functional epimutations are associated with preeclampsia disease status and the identified genes may represent novel biomarkers of disease.</p></div>", "links"=>[], "tags"=>["123 genes", "gene expression", "Altered CpG methylation", "CpG methylation", "placental trophoblast invasion", "preeclampsia disease status", "Preeclamptic Placenta Related", "growth factor beta", "tgf"], "article_id"=>1587775, "categories"=>["Biological Sciences"], "users"=>["Elizabeth Martin", "Paul D. Ray", "Lisa Smeester", "Matthew R. Grace", "Kim Boggess", "Rebecca C. Fry"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0141294.s001", "https://dx.doi.org/10.1371/journal.pone.0141294.s002", "https://dx.doi.org/10.1371/journal.pone.0141294.s003", "https://dx.doi.org/10.1371/journal.pone.0141294.s004", "https://dx.doi.org/10.1371/journal.pone.0141294.s005", "https://dx.doi.org/10.1371/journal.pone.0141294.s006"], "stats"=>{"downloads"=>5, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Epigenetics_and_Preeclampsia_Defining_Functional_Epimutations_in_the_Preeclamptic_Placenta_Related_to_the_TGF_946_Pathway_/1587775", "title"=>"Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-β Pathway", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-28 03:26:59"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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