Parent-of-Origin DNA Methylation Dynamics during Mouse Development
Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/107925 https://orcid.org/0000-0001-5466-859X |
| _version_ | 1826209246455267328 |
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| author | Stelzer, Yonatan Wu, Hao Song, Yuelin Shivalila, Chikdu S. Markoulaki, Styliani Jaenisch, Rudolf |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Stelzer, Yonatan Wu, Hao Song, Yuelin Shivalila, Chikdu S. Markoulaki, Styliani Jaenisch, Rudolf |
| author_sort | Stelzer, Yonatan |
| collection | MIT |
| description | Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults. To test this hypothesis, we targeted a reporter for genomic methylation to the imprinted Dlk1-Dio3 intergenic DMR (IG-DMR) to assess the methylation of both parental alleles at single-cell resolution. Biallelic gain or loss of IG-DMR methylation occurred in a small fraction of mouse embryonic stem cells, significantly affecting developmental potency. Mice carrying the reporter in either parental allele showed striking parent-specific changes in IG-DMR methylation, causing substantial and consistent tissue- and cell-type-dependent signatures in embryos and postnatal animals. Furthermore, dynamics in DNA methylation persisted during adult neurogenesis, resulting in inter-individual diversity. This substantial cell-cell DNA methylation heterogeneity implies that dynamic DNA methylation variations in the adult may be of functional importance. |
| first_indexed | 2024-09-23T14:19:30Z |
| format | Article |
| id | mit-1721.1/107925 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:19:30Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1079252022-10-01T20:38:41Z Parent-of-Origin DNA Methylation Dynamics during Mouse Development Stelzer, Yonatan Wu, Hao Song, Yuelin Shivalila, Chikdu S. Markoulaki, Styliani Jaenisch, Rudolf Massachusetts Institute of Technology. Department of Biology Song, Yuelin Jaenisch, Rudolf Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults. To test this hypothesis, we targeted a reporter for genomic methylation to the imprinted Dlk1-Dio3 intergenic DMR (IG-DMR) to assess the methylation of both parental alleles at single-cell resolution. Biallelic gain or loss of IG-DMR methylation occurred in a small fraction of mouse embryonic stem cells, significantly affecting developmental potency. Mice carrying the reporter in either parental allele showed striking parent-specific changes in IG-DMR methylation, causing substantial and consistent tissue- and cell-type-dependent signatures in embryos and postnatal animals. Furthermore, dynamics in DNA methylation persisted during adult neurogenesis, resulting in inter-individual diversity. This substantial cell-cell DNA methylation heterogeneity implies that dynamic DNA methylation variations in the adult may be of functional importance. National Institutes of Health (HD 045022) Brain & Behavior Research Foundation (grant 22950) 2017-04-06T20:48:28Z 2017-04-06T20:48:28Z 2016-09 2016-09 Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/107925 Stelzer, Yonatan, Hao Wu, Yuelin Song, Chikdu S. Shivalila, Styliani Markoulaki, and Rudolf Jaenisch. “Parent-of-Origin DNA Methylation Dynamics During Mouse Development.” Cell Reports 16, no. 12 (September 2016): 3167–3180. https://orcid.org/0000-0001-5466-859X en_US http://dx.doi.org/10.1016/j.celrep.2016.08.066 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Stelzer, Yonatan Wu, Hao Song, Yuelin Shivalila, Chikdu S. Markoulaki, Styliani Jaenisch, Rudolf Parent-of-Origin DNA Methylation Dynamics during Mouse Development |
| title | Parent-of-Origin DNA Methylation Dynamics during Mouse Development |
| title_full | Parent-of-Origin DNA Methylation Dynamics during Mouse Development |
| title_fullStr | Parent-of-Origin DNA Methylation Dynamics during Mouse Development |
| title_full_unstemmed | Parent-of-Origin DNA Methylation Dynamics during Mouse Development |
| title_short | Parent-of-Origin DNA Methylation Dynamics during Mouse Development |
| title_sort | parent of origin dna methylation dynamics during mouse development |
| url | http://hdl.handle.net/1721.1/107925 https://orcid.org/0000-0001-5466-859X |
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