DNA methylation modulated genetic variant effect on gene transcriptional regulation
Abstract Background Expression quantitative trait locus (eQTL) analysis has emerged as an important tool in elucidating the link between genetic variants and gene expression, thereby bridging the gap between risk SNPs and associated diseases. We recently identified and validated a specific case wher...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-023-03130-5 |
| _version_ | 1797397976748916736 |
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| author | Yong Zeng Rahi Jain Magnus Lam Musaddeque Ahmed Haiyang Guo Wenjie Xu Yuan Zhong Gong-Hong Wei Wei Xu Housheng Hansen He |
| author_facet | Yong Zeng Rahi Jain Magnus Lam Musaddeque Ahmed Haiyang Guo Wenjie Xu Yuan Zhong Gong-Hong Wei Wei Xu Housheng Hansen He |
| author_sort | Yong Zeng |
| collection | DOAJ |
| description | Abstract Background Expression quantitative trait locus (eQTL) analysis has emerged as an important tool in elucidating the link between genetic variants and gene expression, thereby bridging the gap between risk SNPs and associated diseases. We recently identified and validated a specific case where the methylation of a CpG site influences the relationship between the genetic variant and gene expression. Results Here, to systematically evaluate this regulatory mechanism, we develop an extended eQTL mapping method, termed DNA methylation modulated eQTL (memo-eQTL). Applying this memo-eQTL mapping method to 128 normal prostate samples enables identification of 1063 memo-eQTLs, the majority of which are not recognized as conventional eQTLs in the same cohort. We observe that the methylation of the memo-eQTL CpG sites can either enhance or insulate the interaction between SNP and gene expression by altering CTCF-based chromatin 3D structure. Conclusions This study demonstrates the prevalence of memo-eQTLs paving the way to identify novel causal genes for traits or diseases associated with genetic variations. |
| first_indexed | 2024-03-09T01:18:02Z |
| format | Article |
| id | doaj.art-ddab9b98b99f4849a657d1ce5da1b112 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-03-09T01:18:02Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-ddab9b98b99f4849a657d1ce5da1b1122023-12-10T12:20:50ZengBMCGenome Biology1474-760X2023-12-0124111510.1186/s13059-023-03130-5DNA methylation modulated genetic variant effect on gene transcriptional regulationYong Zeng0Rahi Jain1Magnus Lam2Musaddeque Ahmed3Haiyang Guo4Wenjie Xu5Yuan Zhong6Gong-Hong Wei7Wei Xu8Housheng Hansen He9Princess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkDepartment of Clinical Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong UniversityMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan UniversityPrincess Margaret Cancer Centre, University Health NetworkMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan UniversityDalla Lana School of Public Health, University of TorontoPrincess Margaret Cancer Centre, University Health NetworkAbstract Background Expression quantitative trait locus (eQTL) analysis has emerged as an important tool in elucidating the link between genetic variants and gene expression, thereby bridging the gap between risk SNPs and associated diseases. We recently identified and validated a specific case where the methylation of a CpG site influences the relationship between the genetic variant and gene expression. Results Here, to systematically evaluate this regulatory mechanism, we develop an extended eQTL mapping method, termed DNA methylation modulated eQTL (memo-eQTL). Applying this memo-eQTL mapping method to 128 normal prostate samples enables identification of 1063 memo-eQTLs, the majority of which are not recognized as conventional eQTLs in the same cohort. We observe that the methylation of the memo-eQTL CpG sites can either enhance or insulate the interaction between SNP and gene expression by altering CTCF-based chromatin 3D structure. Conclusions This study demonstrates the prevalence of memo-eQTLs paving the way to identify novel causal genes for traits or diseases associated with genetic variations.https://doi.org/10.1186/s13059-023-03130-5SNPCTCFmeCpGeQTLMemo-eQTLChromatin 3D structure |
| spellingShingle | Yong Zeng Rahi Jain Magnus Lam Musaddeque Ahmed Haiyang Guo Wenjie Xu Yuan Zhong Gong-Hong Wei Wei Xu Housheng Hansen He DNA methylation modulated genetic variant effect on gene transcriptional regulation Genome Biology SNP CTCF meCpG eQTL Memo-eQTL Chromatin 3D structure |
| title | DNA methylation modulated genetic variant effect on gene transcriptional regulation |
| title_full | DNA methylation modulated genetic variant effect on gene transcriptional regulation |
| title_fullStr | DNA methylation modulated genetic variant effect on gene transcriptional regulation |
| title_full_unstemmed | DNA methylation modulated genetic variant effect on gene transcriptional regulation |
| title_short | DNA methylation modulated genetic variant effect on gene transcriptional regulation |
| title_sort | dna methylation modulated genetic variant effect on gene transcriptional regulation |
| topic | SNP CTCF meCpG eQTL Memo-eQTL Chromatin 3D structure |
| url | https://doi.org/10.1186/s13059-023-03130-5 |
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