Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice
Objective: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. Methods: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation profiling of gene promoters to determine the differential...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Arán Ediciones, S. L.
2014-07-01
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| Series: | Nutrición Hospitalaria |
| Subjects: | |
| Online Access: | http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0212-16112014000800006&lng=en&tlng=en |
| _version_ | 1818505078965796864 |
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| author | Fan Chaonan Dong Hua Yan Kesong Shen Wenwen Wang Cui Xia Lulu Zhan Dawei Qi Kemin |
| author_facet | Fan Chaonan Dong Hua Yan Kesong Shen Wenwen Wang Cui Xia Lulu Zhan Dawei Qi Kemin |
| author_sort | Fan Chaonan |
| collection | DOAJ |
| description | Objective: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. Methods: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation profiling of gene promoters to determine the differentially methylated genes using methylated DNA immunoprecipitation followed by hybridization to the NimbleGen MM8 CpG plus Promoter Microarray. We further integrated epigenomics data with gene expression profiling to identify promoters exhibiting an association between methylation status and the expression of downstream genes. Results: A total of 24 hypermethylated promoters and 42 hypomethylated promoters in epididymal fat were selected as methylation markers, which were associated with downregulated and upregulated gene expression, respectively. The promoter methylation and differential gene expression of three markers (Mmp2, Foxj3 and Ube2q2) in the fat were validated by sequencing bisulfite-modified DNA and real-time reverse transcriptase PCR. The genes with these differentially methylated promoters and the associated transcriptional expression in the fat were primarily involved in biological activities in lipid metabolism and storage, cellular differentiation, immunity and the pathogenesis of obesity-related complications. Conclusions: This study represents the first effort to determine methylation markers in obese mice that may regulate gene transcription in obesity. Our approach has potential relevance for clinical applications by identifying markers useful in elucidating the mechanisms of obesity pathogenesis and its complications. |
| first_indexed | 2024-12-10T21:45:51Z |
| format | Article |
| id | doaj.art-89a83c8506ec4947840be334596c1156 |
| institution | Directory Open Access Journal |
| issn | 0212-1611 |
| language | English |
| last_indexed | 2024-12-10T21:45:51Z |
| publishDate | 2014-07-01 |
| publisher | Arán Ediciones, S. L. |
| record_format | Article |
| series | Nutrición Hospitalaria |
| spelling | doaj.art-89a83c8506ec4947840be334596c11562022-12-22T01:32:23ZengArán Ediciones, S. L.Nutrición Hospitalaria0212-16112014-07-01301425210.3305/nh.2014.30.1.7521S0212-16112014000800006Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese miceFan Chaonan0Dong Hua1Yan Kesong2Shen Wenwen3Wang Cui4Xia Lulu5Zhan Dawei6Qi Kemin7Beijing Pediatric Research InstituteBeijing Pediatric Research InstituteGeneral Hospital of the People´s Liberation ArmyBeijing Pediatric Research InstituteBeijing Pediatric Research InstituteBeijing Pediatric Research InstituteGeneral Hospital of the People´s Liberation ArmyBeijing Pediatric Research InstituteObjective: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. Methods: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation profiling of gene promoters to determine the differentially methylated genes using methylated DNA immunoprecipitation followed by hybridization to the NimbleGen MM8 CpG plus Promoter Microarray. We further integrated epigenomics data with gene expression profiling to identify promoters exhibiting an association between methylation status and the expression of downstream genes. Results: A total of 24 hypermethylated promoters and 42 hypomethylated promoters in epididymal fat were selected as methylation markers, which were associated with downregulated and upregulated gene expression, respectively. The promoter methylation and differential gene expression of three markers (Mmp2, Foxj3 and Ube2q2) in the fat were validated by sequencing bisulfite-modified DNA and real-time reverse transcriptase PCR. The genes with these differentially methylated promoters and the associated transcriptional expression in the fat were primarily involved in biological activities in lipid metabolism and storage, cellular differentiation, immunity and the pathogenesis of obesity-related complications. Conclusions: This study represents the first effort to determine methylation markers in obese mice that may regulate gene transcription in obesity. Our approach has potential relevance for clinical applications by identifying markers useful in elucidating the mechanisms of obesity pathogenesis and its complications.http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0212-16112014000800006&lng=en&tlng=enObesidadMetilación pangenómica del ADNExpresión génicaDieta rica en grasaRatón |
| spellingShingle | Fan Chaonan Dong Hua Yan Kesong Shen Wenwen Wang Cui Xia Lulu Zhan Dawei Qi Kemin Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice Nutrición Hospitalaria Obesidad Metilación pangenómica del ADN Expresión génica Dieta rica en grasa Ratón |
| title | Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice |
| title_full | Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice |
| title_fullStr | Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice |
| title_full_unstemmed | Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice |
| title_short | Genome-wide screen of promoter methylation identifies novel markers in diet-induced obese mice |
| title_sort | genome wide screen of promoter methylation identifies novel markers in diet induced obese mice |
| topic | Obesidad Metilación pangenómica del ADN Expresión génica Dieta rica en grasa Ratón |
| url | http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0212-16112014000800006&lng=en&tlng=en |
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