DNA methylation and DNA methyltransferases
Abstract The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at le...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-017-0130-8 |
| _version_ | 1817976113056448512 |
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| author | John R. Edwards Olya Yarychkivska Mathieu Boulard Timothy H. Bestor |
| author_facet | John R. Edwards Olya Yarychkivska Mathieu Boulard Timothy H. Bestor |
| author_sort | John R. Edwards |
| collection | DOAJ |
| description | Abstract The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes. |
| first_indexed | 2024-04-13T21:59:08Z |
| format | Article |
| id | doaj.art-49017be66fca4553a952b2fbc76f1092 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-04-13T21:59:08Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-49017be66fca4553a952b2fbc76f10922022-12-22T02:28:10ZengBMCEpigenetics & Chromatin1756-89352017-05-0110111010.1186/s13072-017-0130-8DNA methylation and DNA methyltransferasesJohn R. Edwards0Olya Yarychkivska1Mathieu Boulard2Timothy H. Bestor3Center for Pharmacogenomics, Department of Medicine, Washington University School of MedicineDepartment of Genetics and Development, College of Physicians and Surgeons of Columbia UniversityDepartment of Genetics and Development, College of Physicians and Surgeons of Columbia UniversityDepartment of Genetics and Development, College of Physicians and Surgeons of Columbia UniversityAbstract The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes.http://link.springer.com/article/10.1186/s13072-017-0130-8EpigeneticsDNA cytosine methylationMammalian DNA methyltransferasesMethylation dynamicsMethylation-related human diseases |
| spellingShingle | John R. Edwards Olya Yarychkivska Mathieu Boulard Timothy H. Bestor DNA methylation and DNA methyltransferases Epigenetics & Chromatin Epigenetics DNA cytosine methylation Mammalian DNA methyltransferases Methylation dynamics Methylation-related human diseases |
| title | DNA methylation and DNA methyltransferases |
| title_full | DNA methylation and DNA methyltransferases |
| title_fullStr | DNA methylation and DNA methyltransferases |
| title_full_unstemmed | DNA methylation and DNA methyltransferases |
| title_short | DNA methylation and DNA methyltransferases |
| title_sort | dna methylation and dna methyltransferases |
| topic | Epigenetics DNA cytosine methylation Mammalian DNA methyltransferases Methylation dynamics Methylation-related human diseases |
| url | http://link.springer.com/article/10.1186/s13072-017-0130-8 |
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