An Alu Element–Associated Hypermethylation Variant of the POMC Gene Is Associated with Childhood Obesity
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{"title"=>"An alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity", "type"=>"journal", "authors"=>[{"first_name"=>"Peter", "last_name"=>"Kuehnen", "scopus_author_id"=>"26021303700"}, {"first_name"=>"Mona", "last_name"=>"Mischke", "scopus_author_id"=>"55164156600"}, {"first_name"=>"Susanna", "last_name"=>"Wiegand", "scopus_author_id"=>"7004864644"}, {"first_name"=>"Christine", "last_name"=>"Sers", "scopus_author_id"=>"6603713187"}, {"first_name"=>"Bernhard", "last_name"=>"Horsthemke", "scopus_author_id"=>"56186820300"}, {"first_name"=>"Susanne", "last_name"=>"Lau", "scopus_author_id"=>"7401596413"}, {"first_name"=>"Thomas", "last_name"=>"Keil", "scopus_author_id"=>"35292287200"}, {"first_name"=>"Young Ae", "last_name"=>"Lee", "scopus_author_id"=>"57060820400"}, {"first_name"=>"Annette", "last_name"=>"Grueters", "scopus_author_id"=>"24447989900"}, {"first_name"=>"Heiko", "last_name"=>"Krude", "scopus_author_id"=>"6701310661"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84859226938", "doi"=>"10.1371/journal.pgen.1002543", "sgr"=>"84859226938", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"22438814", "issn"=>"15537390", "pui"=>"364556449"}, "id"=>"dd27b208-21ae-31cc-8870-ea028899d4ce", "abstract"=>"The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the POMC locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron 2-exon 3 boundary of the POMC gene by bisulphite sequencing that was significantly associated with obesity. POMC exon 3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the POMC transcript. Since intron 2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon 3 methylation variant seems to result from an Alu element-triggered default state of methylation boundary definition. Exon 3 hypermethylation in the POMC locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity.", "link"=>"http://www.mendeley.com/research/alu-elementassociated-hypermethylation-variant-pomc-gene-associated-childhood-obesity", "reader_count"=>89, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>22, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>2, "Student > Master"=>8, "Other"=>10, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>22, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>2, "Student > Master"=>8, "Other"=>10, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>6, "Nursing and Health Professions"=>2, "Medicine and Dentistry"=>15, "Agricultural and Biological Sciences"=>55, "Neuroscience"=>1, "Physics and Astronomy"=>2, "Psychology"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>55}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>2, "Mexico"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/341612", "https://ndownloader.figshare.com/files/341672", "https://ndownloader.figshare.com/files/341723", "https://ndownloader.figshare.com/files/341760", "https://ndownloader.figshare.com/files/341808", "https://ndownloader.figshare.com/files/341857"], "description"=>"<div><p>The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the <em>POMC</em> locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron2–exon3 boundary of the <em>POMC</em> gene by bisulphite sequencing that was significantly associated with obesity. <em>POMC</em> exon3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the <em>POMC</em> transcript. Since intron2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon3 methylation variant seems to result from an Alu element–triggered default state of methylation boundary definition. Exon3 hypermethylation in the <em>POMC</em> locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity.</p> </div>", "links"=>[], "tags"=>["alu", "hypermethylation", "variant", "obesity"], "article_id"=>127522, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.s001", "https://dx.doi.org/10.1371/journal.pgen.1002543.s002", "https://dx.doi.org/10.1371/journal.pgen.1002543.s003", "https://dx.doi.org/10.1371/journal.pgen.1002543.s004", "https://dx.doi.org/10.1371/journal.pgen.1002543.s005", "https://dx.doi.org/10.1371/journal.pgen.1002543.s006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/An_Alu_Element_Associated_Hypermethylation_Variant_of_the_POMC_Gene_Is_Associated_with_Childhood_Obesity/127522", "title"=>"An Alu Element–Associated Hypermethylation Variant of the <em>POMC</em> Gene Is Associated with Childhood Obesity", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-03-15 02:05:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/666689"], "description"=>"<p>Analysis example of the DNA methylation pattern of human peripheral blood cells (PBC) from a normal weight individual after sequencing of 10 different clones of the PCR amplification product. Filled cycles represent methylated CpGs, open cycles non-methylated CpG positions, which are numbered according to their relative position to the start of the next exon. Alu element positions and P300 binding site are marked.</p>", "links"=>[], "tags"=>["cpg", "methylation"], "article_id"=>337169, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_POMC_CpG_methylation_pattern_of_CpG_island_1_and_2_/337169", "title"=>"<i>POMC</i> CpG methylation pattern of CpG island 1 and 2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 01:59:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/666800"], "description"=>"<p>CpG positions are numbered according to their relative position to the next exon start.</p>", "links"=>[], "tags"=>["dna", "methylation", "cpg", "normal-weight", "adolescents", "laser-microdissected", "msh", "cells", "arcuate", "nucleus", "newborn", "samples"], "article_id"=>337263, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_POMC_DNA_methylation_pattern_of_CpG_island_1_and_2_in_normal_weight_adolescents_n_12_laser_microdissected_MSH_positive_cells_of_the_human_arcuate_nucleus_n_5_and_human_newborn_samples_n_8_/337263", "title"=>"<i>POMC</i> DNA methylation pattern of CpG island 1 and 2 in normal-weight adolescents (n = 12), laser-microdissected MSH positive cells of the human arcuate nucleus (n = 5) and human newborn samples (n = 8).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:01:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/666941"], "description"=>"<p>A, B, C agarose-embedded DNA was analysed by bisulphite sequencing. In D, E, F DNA was bisulphite treated in a non-agarose-bead protocol. A/D Diagram of the DNA methylation score (%) of <i>POMC</i> CpG island 2 within PBC of normal weight (red) and obese individuals (blue) (p<0,001). CpG positions are numbered according to their relative position to the next exon start. B/E Box plots analysis represents the statistic differences from the mean CpG methylation score (%) of CpG position −4 to +6 in normal weight individuals versus obese patients. C/F Percent of normal weight (red) and obese (blue) individuals, who showed DNA methylation at the annotated single CpG position (−1 to +5) in relation to the analysed number of samples.</p>", "links"=>[], "tags"=>["dna", "methylation", "was", "analysed", "bisulphite", "protocols"], "article_id"=>337416, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_DNA_methylation_was_analysed_with_two_different_bisulphite_based_protocols_in_two_independent_cohorts_/337416", "title"=>"The DNA methylation was analysed with two different bisulphite based protocols in two independent cohorts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:03:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/667059"], "description"=>"<p>Each line represents one individual course of DNA methylation score prior to and after weight gain.</p>", "links"=>[], "tags"=>["dna", "methylation", "obesity", "21", "mas"], "article_id"=>337533, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_analysis_of_POMC_DNA_methylation_score_CpG_position_4_to_6_before_and_after_the_development_of_obesity_in_altogether_21_participants_of_the_MAS_birth_cohort_/337533", "title"=>"Longitudinal analysis of <i>POMC</i> DNA methylation score (%) (CpG position −4 to +6) before and after the development of obesity in altogether 21 participants of the MAS birth cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:05:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/667141"], "description"=>"<p>(A) <i>POMC</i> intron2 exon3 genomic sequence with annotated ChIP primer localization and P300 binding site. (B) P300 ChIP assay was performed at three independent occasions within human peripheral blood cells. <i>POMC</i> fragment was amplified with two different primer pairs (fragment 1 and 2). Confirmation of a published P300 binding site within the insulin gene promoter in β-TC3 cells was used as a positive control <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002543#pgen.1002543-Chakrabarti1\" target=\"_blank\">[34]</a> (<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002543#pgen.1002543.s005\" target=\"_blank\">Figure S5</a>). (C) Real time PCR analysis (PCR fragment 2) of the P300 ChIP results of 4 obese patients with a hypermethylation variant and 6 individuals with hypomethylated intron 2-exon 3 intersection at <i>POMC</i> CpG island 2. (D) Real-time <i>POMC</i> PCR (<i>POMC</i> exon 2–3 and <i>POMC</i> exon3) of cDNA extracted from PBC of hypomethylated normal weight individuals (n = 20), hypermethylated obese patients (n = 20), and obese individuals without the hypermethylated variant (n = 20) reveal reduced POMC gene expression in the hypermethylated samples.</p>", "links"=>[], "tags"=>["intron2", "exon3", "genomic", "p300", "Real-time", "pcr"], "article_id"=>337612, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_POMC_intron2_exon3_genomic_sequence_P300_ChIP_assay_real_time_PCR_analysis_and_real_time_POMC_PCR_/337612", "title"=>"<i>POMC</i> intron2 exon3 genomic sequence, P300 ChIP assay, real-time PCR analysis, and real-time <i>POMC</i> PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:06:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/667239"], "description"=>"<p>In (A) normal-weight human individuals (n = 36), (B) chimpanzee PBC (n = 2), (C) lemur PBC (n = 3), and (D) mice PBC (n = 3). CpG positions are numbered according to their relative position to the exon 3 start.</p>", "links"=>[], "tags"=>["methylation", "dna", "bisulphite", "genomic", "sequencing", "cpg"], "article_id"=>337716, "categories"=>["Chemistry", "Genetics"], "users"=>["Peter Kuehnen", "Mona Mischke", "Susanna Wiegand", "Christine Sers", "Bernhard Horsthemke", "Susanne Lau", "Thomas Keil", "Young-Ae Lee", "Annette Grueters", "Heiko Krude"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002543.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Species_specific_POMC_methylation_pattern_POMC_DNA_methylation_pattern_after_bisulphite_genomic_sequencing_of_CpG_island_2_/337716", "title"=>"Species-specific <i>POMC</i> methylation pattern <i>POMC</i> DNA methylation pattern after bisulphite genomic sequencing of CpG island 2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-15 02:08:36"}

PMC Usage Stats | Further Information

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