Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci
To assess the impact of genetic variation in regulatory loci on human health, we constructed a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite seque...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2019
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| Online Access: | https://hdl.handle.net/1721.1/121218 |
| _version_ | 1811092531626115072 |
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| author | Altshuler, Robert Charles Onuchic, Vitor Lurie, Eugene Carrero, Ivenise Pawliczek, Piotr Patel, Ronak Y. Rozowsky, Joel Galeev, Timur Huang, Zhuoyi Harris, R. Alan Coarfa, Cristian Ashmore, Lillian Bertol, Jessica W. Fakhouri, Walid D. Yu, Fuli Kellis, Manolis Gerstein, Mark Milosavljevic, Aleksandar |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Altshuler, Robert Charles Onuchic, Vitor Lurie, Eugene Carrero, Ivenise Pawliczek, Piotr Patel, Ronak Y. Rozowsky, Joel Galeev, Timur Huang, Zhuoyi Harris, R. Alan Coarfa, Cristian Ashmore, Lillian Bertol, Jessica W. Fakhouri, Walid D. Yu, Fuli Kellis, Manolis Gerstein, Mark Milosavljevic, Aleksandar |
| author_sort | Altshuler, Robert Charles |
| collection | MIT |
| description | To assess the impact of genetic variation in regulatory loci on human health, we constructed a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite sequencing of 49 methylomes revealed sequence-dependent CpG methylation imbalances at thousands of heterozygous regulatory loci. Such loci are enriched for stochastic switching, which is defined as random transitions between fully methylated and unmethylated states of DNA.The methylation imbalances at thousands of loci are explainable by different relative frequencies of the methylated and unmethylated states for the two alleles. Further analyses provided a unifying model that links sequence-dependent allelic imbalances of the epigenome, stochastic switching at gene regulatory loci, and disease-associated genetic variation. |
| first_indexed | 2024-09-23T15:19:42Z |
| format | Article |
| id | mit-1721.1/121218 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:19:42Z |
| publishDate | 2019 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1212182022-09-29T14:14:56Z Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci Altshuler, Robert Charles Onuchic, Vitor Lurie, Eugene Carrero, Ivenise Pawliczek, Piotr Patel, Ronak Y. Rozowsky, Joel Galeev, Timur Huang, Zhuoyi Harris, R. Alan Coarfa, Cristian Ashmore, Lillian Bertol, Jessica W. Fakhouri, Walid D. Yu, Fuli Kellis, Manolis Gerstein, Mark Milosavljevic, Aleksandar Massachusetts Institute of Technology. Department of Biology To assess the impact of genetic variation in regulatory loci on human health, we constructed a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite sequencing of 49 methylomes revealed sequence-dependent CpG methylation imbalances at thousands of heterozygous regulatory loci. Such loci are enriched for stochastic switching, which is defined as random transitions between fully methylated and unmethylated states of DNA.The methylation imbalances at thousands of loci are explainable by different relative frequencies of the methylated and unmethylated states for the two alleles. Further analyses provided a unifying model that links sequence-dependent allelic imbalances of the epigenome, stochastic switching at gene regulatory loci, and disease-associated genetic variation. 2019-06-07T14:55:32Z 2019-06-07T14:55:32Z 2018-09 2017-10 2019-06-07T14:13:56Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 https://hdl.handle.net/1721.1/121218 Onuchic, Vitor et al. "Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci." Science 361, 6409 (September 2018): eaar3146 © American Association for the Advancement of Science en http://dx.doi.org/10.1126/SCIENCE.AAR3146 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Altshuler, Robert Charles Onuchic, Vitor Lurie, Eugene Carrero, Ivenise Pawliczek, Piotr Patel, Ronak Y. Rozowsky, Joel Galeev, Timur Huang, Zhuoyi Harris, R. Alan Coarfa, Cristian Ashmore, Lillian Bertol, Jessica W. Fakhouri, Walid D. Yu, Fuli Kellis, Manolis Gerstein, Mark Milosavljevic, Aleksandar Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci |
| title | Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci |
| title_full | Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci |
| title_fullStr | Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci |
| title_full_unstemmed | Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci |
| title_short | Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci |
| title_sort | allele specific epigenome maps reveal sequence dependent stochastic switching at regulatory loci |
| url | https://hdl.handle.net/1721.1/121218 |
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