Sparse conserved under-methylated CpGs are associated with high-order chromatin structure
Abstract Background Whole-genome bisulfite sequencing (WGBS) is the gold standard for studying landscape DNA methylation. Current computational methods for WGBS are mainly designed for gene regulatory regions with multiple under-methylated CpGs (UMCs), such as promoters and enhancers. Results To rel...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Genome Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s13059-017-1296-x |
| _version_ | 1818853507366649856 |
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| author | Xueqiu Lin Jianzhong Su Kaifu Chen Benjamin Rodriguez Wei Li |
| author_facet | Xueqiu Lin Jianzhong Su Kaifu Chen Benjamin Rodriguez Wei Li |
| author_sort | Xueqiu Lin |
| collection | DOAJ |
| description | Abstract Background Whole-genome bisulfite sequencing (WGBS) is the gold standard for studying landscape DNA methylation. Current computational methods for WGBS are mainly designed for gene regulatory regions with multiple under-methylated CpGs (UMCs), such as promoters and enhancers. Results To reliably predict the functional importance of single isolated UMCs across the genome, which is usually not achievable using traditional methods, we develop a multi-sample-based method. We identified 9421 sparse conserved under-methylated CpGs (scUMCs) from 31 high-quality methylomes, which are enriched in distal interacting anchor regions co-occupied by multiple chromatin-loop factors and are flanked by highly methylated CpGs. Moreover, cell lineage-specific scUMCs are associated with essential developmental genes, regulators of cell differentiation, and chromatin remodeling enzymes. Dynamic methylation levels of scUMCs correlate with the intensity of chromatin interactions and binding of looping factors as well as patterns of gene expression. Conclusions We introduce an innovative computational method for the identification of scUMCs, which are novel epigenetic features associated with high-order chromatin structure, opening new directions in the study of the inter-relationships between DNA methylation and chromatin structure. |
| first_indexed | 2024-12-19T07:37:55Z |
| format | Article |
| id | doaj.art-16523061bec345eebbd6d305ab48651d |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-19T07:37:55Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-16523061bec345eebbd6d305ab48651d2022-12-21T20:30:32ZengBMCGenome Biology1474-760X2017-08-0118111010.1186/s13059-017-1296-xSparse conserved under-methylated CpGs are associated with high-order chromatin structureXueqiu Lin0Jianzhong Su1Kaifu Chen2Benjamin Rodriguez3Wei Li4Division of Biostatistics, Dan L Duncan Cancer Center, Baylor College of MedicineDivision of Biostatistics, Dan L Duncan Cancer Center, Baylor College of MedicineDivision of Biostatistics, Dan L Duncan Cancer Center, Baylor College of MedicineDivision of Biostatistics, Dan L Duncan Cancer Center, Baylor College of MedicineDivision of Biostatistics, Dan L Duncan Cancer Center, Baylor College of MedicineAbstract Background Whole-genome bisulfite sequencing (WGBS) is the gold standard for studying landscape DNA methylation. Current computational methods for WGBS are mainly designed for gene regulatory regions with multiple under-methylated CpGs (UMCs), such as promoters and enhancers. Results To reliably predict the functional importance of single isolated UMCs across the genome, which is usually not achievable using traditional methods, we develop a multi-sample-based method. We identified 9421 sparse conserved under-methylated CpGs (scUMCs) from 31 high-quality methylomes, which are enriched in distal interacting anchor regions co-occupied by multiple chromatin-loop factors and are flanked by highly methylated CpGs. Moreover, cell lineage-specific scUMCs are associated with essential developmental genes, regulators of cell differentiation, and chromatin remodeling enzymes. Dynamic methylation levels of scUMCs correlate with the intensity of chromatin interactions and binding of looping factors as well as patterns of gene expression. Conclusions We introduce an innovative computational method for the identification of scUMCs, which are novel epigenetic features associated with high-order chromatin structure, opening new directions in the study of the inter-relationships between DNA methylation and chromatin structure.http://link.springer.com/article/10.1186/s13059-017-1296-xSparse conserved under-methylated CpGWhole-genome bisulfite sequencingMulti-sample-based methodChromatin-loop factorsInteracting anchorDNA methylation |
| spellingShingle | Xueqiu Lin Jianzhong Su Kaifu Chen Benjamin Rodriguez Wei Li Sparse conserved under-methylated CpGs are associated with high-order chromatin structure Genome Biology Sparse conserved under-methylated CpG Whole-genome bisulfite sequencing Multi-sample-based method Chromatin-loop factors Interacting anchor DNA methylation |
| title | Sparse conserved under-methylated CpGs are associated with high-order chromatin structure |
| title_full | Sparse conserved under-methylated CpGs are associated with high-order chromatin structure |
| title_fullStr | Sparse conserved under-methylated CpGs are associated with high-order chromatin structure |
| title_full_unstemmed | Sparse conserved under-methylated CpGs are associated with high-order chromatin structure |
| title_short | Sparse conserved under-methylated CpGs are associated with high-order chromatin structure |
| title_sort | sparse conserved under methylated cpgs are associated with high order chromatin structure |
| topic | Sparse conserved under-methylated CpG Whole-genome bisulfite sequencing Multi-sample-based method Chromatin-loop factors Interacting anchor DNA methylation |
| url | http://link.springer.com/article/10.1186/s13059-017-1296-x |
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