DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation.
In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not full...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-04-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009498 |
| _version_ | 1818590180279320576 |
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| author | Adi Alajem Hava Roth Sofia Ratgauzer Danny Bavli Alex Motzik Shlomtzion Lahav Itay Peled Oren Ram |
| author_facet | Adi Alajem Hava Roth Sofia Ratgauzer Danny Bavli Alex Motzik Shlomtzion Lahav Itay Peled Oren Ram |
| author_sort | Adi Alajem |
| collection | DOAJ |
| description | In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1- versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems. |
| first_indexed | 2024-12-16T09:52:26Z |
| format | Article |
| id | doaj.art-bac1e76cae9c4b6ab60138d1fd9c7c91 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-16T09:52:26Z |
| publishDate | 2021-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-bac1e76cae9c4b6ab60138d1fd9c7c912022-12-21T22:36:00ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-04-01174e100949810.1371/journal.pgen.1009498DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation.Adi AlajemHava RothSofia RatgauzerDanny BavliAlex MotzikShlomtzion LahavItay PeledOren RamIn mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1- versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.https://doi.org/10.1371/journal.pgen.1009498 |
| spellingShingle | Adi Alajem Hava Roth Sofia Ratgauzer Danny Bavli Alex Motzik Shlomtzion Lahav Itay Peled Oren Ram DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. PLoS Genetics |
| title | DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. |
| title_full | DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. |
| title_fullStr | DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. |
| title_full_unstemmed | DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. |
| title_short | DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. |
| title_sort | dna methylation patterns expose variations in enhancer chromatin modifications during embryonic stem cell differentiation |
| url | https://doi.org/10.1371/journal.pgen.1009498 |
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