Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region
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{"title"=>"Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region", "type"=>"journal", "authors"=>[{"first_name"=>"Matthias", "last_name"=>"Ruebner", "scopus_author_id"=>"57193129957"}, {"first_name"=>"Pamela L.", "last_name"=>"Strissel", "scopus_author_id"=>"6602377465"}, {"first_name"=>"Arif B.", "last_name"=>"Ekici", "scopus_author_id"=>"6603821550"}, {"first_name"=>"Elisabeth", "last_name"=>"Stiegler", "scopus_author_id"=>"23101456300"}, {"first_name"=>"Ulf", "last_name"=>"Dammer", "scopus_author_id"=>"39161147700"}, {"first_name"=>"Tamme W.", "last_name"=>"Goecke", "scopus_author_id"=>"6603667945"}, {"first_name"=>"Florian", "last_name"=>"Faschingbauer", "scopus_author_id"=>"21833745300"}, {"first_name"=>"Fabian B.", "last_name"=>"Fahlbusch", "scopus_author_id"=>"26646410900"}, {"first_name"=>"Matthias W.", "last_name"=>"Beckmann", "scopus_author_id"=>"55581184800"}, {"first_name"=>"Reiner", "last_name"=>"Strick", "scopus_author_id"=>"56032162800"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84874013797", "sgr"=>"84874013797", "pui"=>"368353926", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23457515", "doi"=>"10.1371/journal.pone.0056145"}, "id"=>"21e699ea-aaa2-35da-b0cc-535b87001d79", "abstract"=>"Terminal differentiation of villous cytotrophoblasts (CT) ends in formation of the multinucleated syncytiotrophoblast representing the fetal-maternal interface. Aberrations during this cell-fusion process are associated with Intrauterine Growth Restriction (IUGR), Preeclampsia (PE) and High Elevated Liver and Low Platelets (HELLP) Syndrome. Syncytin-1, the envelope gene of the human Endogenous Retrovirus ERVW-1, is one of the most important genes involved in cell-fusion and showed decreased gene expression during these pathological pregnancies. The aim of this study was to determine the methylation pattern of the entire promoter of ERVW-1 and to correlate these findings with the expression profile of Syncytin-1 in the placental syndromes. 14 isolated villous cytotrophoblasts from control (n = 3), IUGR (n = 3), PE (n = 3), PE/IUGR (n = 3) and HELLP/IUGR (n = 2) placentae were used to determine the mean methylation level (ML) for the ERVW-1 promoter region. ML rose significantly from 29% in control CTs to 49% in IUGR, 53% in PE, 47% in PE/IUGR and 64% in HELLP/IUGR indicating an epigenetic down-regulation of Syncytin-1 by promoter hypermethylation. DNA demethylation of the trophoblast like cell lines BeWo, JEG-3 and JAR with 5-AZA-2'desoxycytidine (AZA) showed an increased Syncytin-1 expression and fusion ability in all cell lines. Promoter activity of the 5'LTR could be inhibited by hypermethylation 42-fold using a luciferase based reporter-gene assay. Finally overexpression of the methyltransferases DNMT3a and LSH could be responsible for a decreased Syncytin-1 expression by promoter hypermethylation of ERVW-1. Our study linked decreased Syncytin-1 expression to an epigenetic hypermethylation of the entire promoter of ERVW-1. Based on our findings we are predicting a broad aberrant epigenetic DNA-methylation pattern in pathological placentae affecting placentogenesis, but also the development of the fetus and the mother during pregnancy.", "link"=>"http://www.mendeley.com/research/reduced-syncytin1-expression-levels-placental-syndromes-correlates-epigenetic-hypermethylation-ervw1", "reader_count"=>44, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>11, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>11, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>17, "Medicine and Dentistry"=>10, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>2, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Chemistry"=>{"Chemistry"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>3, "Brazil"=>1, "Mexico"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/485913"], "description"=>"<div><p>Terminal differentiation of villous cytotrophoblasts (CT) ends in formation of the multinucleated syncytiotrophoblast representing the fetal-maternal interface. Aberrations during this cell-fusion process are associated with Intrauterine Growth Restriction (IUGR), Preeclampsia (PE) and High Elevated Liver and Low Platelets (HELLP) Syndrome. Syncytin-1, the envelope gene of the human Endogenous Retrovirus ERVW-1, is one of the most important genes involved in cell-fusion and showed decreased gene expression during these pathological pregnancies. The aim of this study was to determine the methylation pattern of the entire promoter of ERVW-1 and to correlate these findings with the expression profile of Syncytin-1 in the placental syndromes. 14 isolated villous cytotrophoblasts from control (n = 3), IUGR (n = 3), PE (n = 3), PE/IUGR (n = 3) and HELLP/IUGR (n = 2) placentae were used to determine the mean methylation level (ML) for the ERVW-1 promoter region. ML rose significantly from 29% in control CTs to 49% in IUGR, 53% in PE, 47% in PE/IUGR and 64% in HELLP/IUGR indicating an epigenetic down-regulation of Syncytin-1 by promoter hypermethylation. DNA demethylation of the trophoblast like cell lines BeWo, JEG-3 and JAR with 5-AZA-2′desoxycytidine (AZA) showed an increased Syncytin-1 expression and fusion ability in all cell lines. Promoter activity of the 5′LTR could be inhibited by hypermethylation 42-fold using a luciferase based reporter-gene assay. Finally overexpression of the methyltransferases DNMT3a and LSH could be responsible for a decreased Syncytin-1 expression by promoter hypermethylation of ERVW-1. Our study linked decreased Syncytin-1 expression to an epigenetic hypermethylation of the entire promoter of ERVW-1. Based on our findings we are predicting a broad aberrant epigenetic DNA-methylation pattern in pathological placentae affecting placentogenesis, but also the development of the fetus and the mother during pregnancy.</p> </div>", "links"=>[], "tags"=>["reduced", "syncytin-1", "levels", "placental", "syndromes", "correlates", "epigenetic", "hypermethylation", "ervw-1", "promoter", "region"], "article_id"=>157035, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Reduced_Syncytin_1_Expression_Levels_in_Placental_Syndromes_Correlates_with_Epigenetic_Hypermethylation_of_the_ERVW_1_Promoter_Region__/157035", "title"=>"Reduced Syncytin-1 Expression Levels in Placental Syndromes Correlates with Epigenetic Hypermethylation of the ERVW-1 Promoter Region", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-14 01:57:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/488421"], "description"=>"<p>A) Locus of Syncytin-1 on chromosome 7q21.2 within the ERVW-1 gene. Black needles represent the single CpG sides in the promoter. Arrows mark binding sites for transcription factors ore methyl binding proteins B) All sequenced clones of control (n = 11), IUGR (n = 12), PE (n = 14), PE/IUGR (n = 13) and HELLP/IUGR (n = 17) from one placental trophoblast isolation of each group. White circles represent unmethylated CpGs and black circles methylated CpGs. C) MethylationHeatMap of the promoter region. Mean of three different placentae of each group. Mean of single CpGs are color-coded. From green unmethylated (0%) over red (50% methylated) to black (100% methylated). meanML → mean methylation level of the entire promoter; clones → total analysed clones of each group; Syn1 → mean Syncytin-1 gene expression in mol/ng<sub>cDNA.</sub></p>", "links"=>[], "tags"=>["promoter", "ervw-1"], "article_id"=>158935, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Methylation_Profile_of_the_entire_promoter_of_ERVW_1_in_isolated_trophoblasts_/158935", "title"=>"Methylation Profile of the entire promoter of ERVW-1 in isolated trophoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-14 02:28:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/488611"], "description"=>"<p>A) Expression data of Syncytin-1 in molecules per ng cDNA [mol/ng<sub>cDNA</sub>] and hCG [mlU/ml] for control (blue), AZA (red), TSA (green) and AZA/TSA (violet) treated cell lines and Fusion index [%] of control (blue) and AZA (red) treated cultures. B) For membrane stains of control (blue) and AZA (red) treated cell lines cell membranes were stained with wheat germ agglutinin Alexa594 (red) and nuclei with Hoechst 33342 (blue). White arrows mark syncytia. *P≤0.05; **P≤0.005; bars represent 50 µm.</p>", "links"=>[], "tags"=>["tsa", "trophoblast-like"], "article_id"=>159125, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AZA_and_TSA_treatment_of_trophoblast_like_cell_lines_/159125", "title"=>"AZA and TSA treatment of trophoblast-like cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-14 02:32:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/488748"], "description"=>"<p>The 5′LTR of ERVW-1 was cloned in the pGL3-basic vector and transfected in BeWo cells. 48 hr post transfection cells were analysed. Luciferase activity of the pGL3-basic vector was set to 1. All experiments were repeated at least five times. Histographs show fold-induction to pGL3-basic. (**P<0.005).</p>", "links"=>[], "tags"=>["genetics and genomics", "obstetrics", "developmental biology"], "article_id"=>159260, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Luciferase_Assay_/159260", "title"=>"Luciferase Assay.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-14 02:34:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/488849"], "description"=>"<p>A) Histograph showing fold-change differences to gene expression profile (2<sup>−ΔΔCT</sup>) of control trophoblasts of IUGR, PE, PE/IUGR and HELLP/IUGR (each n = 7). Red line marks gene expression profile of control trophoblasts set to 1. (*P≤0.05). B) Venn diagram showing for each placental syndrome the statistical significant different expressed genes compared to control VCTs. The intersection of all four placental syndromes represents Syncytin-1.</p>", "links"=>[], "tags"=>["syncytin-1", "methyl-binding", "proteins"], "article_id"=>159364, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_profile_of_Syncytin_1_and_methyl_binding_proteins_in_isolated_trophoblasts_/159364", "title"=>"Gene expression profile of Syncytin-1 and methyl-binding proteins in isolated trophoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-14 02:36:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/488911"], "description"=>"<p>GOT: Glutamate-Oxaloacetate-Transaminase; GPT: Glutamate-Pyruvate-Transaminase; LDH: Lactate dehydrogenase;</p><p>Significant changes marked in bold.</p>", "links"=>[], "tags"=>["genetics and genomics", "obstetrics", "developmental biology"], "article_id"=>159424, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_data_/159424", "title"=>"Clinical data.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-14 02:37:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/488944"], "description"=>"<p>SYBR-Green primers for real time PCR.</p>", "links"=>[], "tags"=>["primers"], "article_id"=>159460, "categories"=>["Cell Biology", "Genetics", "Developmental Biology"], "users"=>["Matthias Ruebner", "Pamela L. Strissel", "Arif B. Ekici", "Elisabeth Stiegler", "Ulf Dammer", "Tamme W. Goecke", "Florian Faschingbauer", "Fabian B. Fahlbusch", "Matthias W. Beckmann", "Reiner Strick"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0056145.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SYBR_Green_primers_for_real_time_PCR_/159460", "title"=>"SYBR-Green primers for real time PCR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-14 02:37:40"}

PMC Usage Stats | Further Information

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Relative Metric

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