Alu Elements in ANRIL Non-Coding RNA at Chromosome 9p21 Modulate Atherogenic Cell Functions through Trans-Regulation of Gene Networks
- Publication Date
- July 04, 2013
- Journal
- PLOS Genetics
- Authors
- Lesca M. Holdt, Steve Hoffmann, Kristina Sass, David Langenberger, et al
- Volume
- 9
- Issue
- 7
- Pages
- e1003588
- DOI
- https://dx.plos.org/10.1371/journal.pgen.1003588
- Publisher URL
- http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1003588
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/23861667
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701717
- Europe PMC
- http://europepmc.org/abstract/MED/23861667
- Web of Science
- 000322321100007
- Scopus
- 84880799429
- Mendeley
- http://www.mendeley.com/research/alu-elements-anril-noncoding-rna-chromosome-9p21-modulate-atherogenic-cell-functions-through-transre
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CiteULike | Further Information
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Mendeley | Further Information
{"title"=>"Alu Elements in ANRIL Non-Coding RNA at Chromosome 9p21 Modulate Atherogenic Cell Functions through Trans-Regulation of Gene Networks", "type"=>"journal", "authors"=>[{"first_name"=>"Lesca M.", "last_name"=>"Holdt", "scopus_author_id"=>"21834186100"}, {"first_name"=>"Steve", "last_name"=>"Hoffmann", "scopus_author_id"=>"24471278600"}, {"first_name"=>"Kristina", "last_name"=>"Sass", "scopus_author_id"=>"22434254200"}, {"first_name"=>"David", "last_name"=>"Langenberger", "scopus_author_id"=>"25635871300"}, {"first_name"=>"Markus", "last_name"=>"Scholz", "scopus_author_id"=>"7202888704"}, {"first_name"=>"Knut", "last_name"=>"Krohn", "scopus_author_id"=>"7202378037"}, {"first_name"=>"Knut", "last_name"=>"Finstermeier", "scopus_author_id"=>"21739407800"}, {"first_name"=>"Anika", "last_name"=>"Stahringer", "scopus_author_id"=>"55805414700"}, {"first_name"=>"Wolfgang", "last_name"=>"Wilfert", "scopus_author_id"=>"12775940500"}, {"first_name"=>"Frank", "last_name"=>"Beutner", "scopus_author_id"=>"23979611000"}, {"first_name"=>"Stephan", "last_name"=>"Gielen", "scopus_author_id"=>"7005725390"}, {"first_name"=>"Gerhard", "last_name"=>"Schuler", "scopus_author_id"=>"7202657026"}, {"first_name"=>"Gabor", "last_name"=>"Gäbel", "scopus_author_id"=>"7005722531"}, {"first_name"=>"Hendrik", "last_name"=>"Bergert", "scopus_author_id"=>"6603408936"}, {"first_name"=>"Ingo", "last_name"=>"Bechmann", "scopus_author_id"=>"7003528377"}, {"first_name"=>"Peter F.", "last_name"=>"Stadler", "scopus_author_id"=>"7102702401"}, {"first_name"=>"Joachim", "last_name"=>"Thiery", "scopus_author_id"=>"55737881700"}, {"first_name"=>"Daniel", "last_name"=>"Teupser", "scopus_author_id"=>"6603802932"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-84880799429", "sgr"=>"84880799429", "pui"=>"369438587", "isbn"=>"1553-7390", "pmid"=>"23861667", "doi"=>"10.1371/journal.pgen.1003588"}, "id"=>"cbb1609a-7269-3f13-92e7-7edc3d2ca8f0", "abstract"=>"The chromosome 9p21 (Chr9p21) locus of coronary artery disease has been identified in the first surge of genome-wide association and is the strongest genetic factor of atherosclerosis known today. Chr9p21 encodes the long non-coding RNA (ncRNA) antisense non-coding RNA in the INK4 locus (ANRIL). ANRIL expression is associated with the Chr9p21 genotype and correlated with atherosclerosis severity. Here, we report on the molecular mechanisms through which ANRIL regulates target-genes in trans, leading to increased cell proliferation, increased cell adhesion and decreased apoptosis, which are all essential mechanisms of atherogenesis. Importantly, trans-regulation was dependent on Alu motifs, which marked the promoters of ANRIL target genes and were mirrored in ANRIL RNA transcripts. ANRIL bound Polycomb group proteins that were highly enriched in the proximity of Alu motifs across the genome and were recruited to promoters of target genes upon ANRIL over-expression. The functional relevance of Alu motifs in ANRIL was confirmed by deletion and mutagenesis, reversing trans-regulation and atherogenic cell functions. ANRIL-regulated networks were confirmed in 2280 individuals with and without coronary artery disease and functionally validated in primary cells from patients carrying the Chr9p21 risk allele. Our study provides a molecular mechanism for pro-atherogenic effects of ANRIL at Chr9p21 and suggests a novel role for Alu elements in epigenetic gene regulation by long ncRNAs.", "link"=>"http://www.mendeley.com/research/alu-elements-anril-noncoding-rna-chromosome-9p21-modulate-atherogenic-cell-functions-through-transre", "reader_count"=>133, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>10, "Researcher"=>40, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>36, "Student > Postgraduate"=>5, "Student > Master"=>17, "Other"=>4, "Student > Bachelor"=>4, "Lecturer"=>2, "Professor"=>8}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>10, "Researcher"=>40, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>36, "Student > Postgraduate"=>5, "Student > Master"=>17, "Other"=>4, "Student > Bachelor"=>4, "Lecturer"=>2, "Professor"=>8}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>36, "Agricultural and Biological Sciences"=>63, "Medicine and Dentistry"=>17, "Arts and Humanities"=>1, "Neuroscience"=>3, "Physics and Astronomy"=>1, "Computer Science"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Neuroscience"=>{"Neuroscience"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>63}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>36}, "Unspecified"=>{"Unspecified"=>8}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Iran"=>1, "United States"=>1, "Norway"=>1, "China"=>1, "Finland"=>1, "Denmark"=>1, "United Kingdom"=>1}, "group_count"=>5}CrossRef
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PMC Usage Stats | Further Information
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Relative Metric
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