dc.contributor.author | Rimoldi, M | en_US |
dc.contributor.author | Wang, N | en_US |
dc.contributor.author | Zhang, J | en_US |
dc.contributor.author | Villar, D | en_US |
dc.contributor.author | Odom, DT | en_US |
dc.contributor.author | Taipale, J | en_US |
dc.contributor.author | Flicek, P | en_US |
dc.contributor.author | Roller, M | en_US |
dc.date.accessioned | 2024-06-10T11:05:39Z | |
dc.date.available | 2024-03-15 | en_US |
dc.date.issued | 2024-06-06 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/97366 | |
dc.description.abstract | BACKGROUND: DNA methylation is an important epigenetic modification which has numerous roles in modulating genome function. Its levels are spatially correlated across the genome, typically high in repressed regions but low in transcription factor (TF) binding sites and active regulatory regions. However, the mechanisms establishing genome-wide and TF binding site methylation patterns are still unclear. RESULTS: Here we use a comparative approach to investigate the association of DNA methylation to TF binding evolution in mammals. Specifically, we experimentally profile DNA methylation and combine this with published occupancy profiles of five distinct TFs (CTCF, CEBPA, HNF4A, ONECUT1, FOXA1) in the liver of five mammalian species (human, macaque, mouse, rat, dog). TF binding sites are lowly methylated, but they often also have intermediate methylation levels. Furthermore, biding sites are influenced by the methylation status of CpGs in their wider binding regions even when CpGs are absent from the core binding motif. Employing a classification and clustering approach, we extract distinct and species-conserved patterns of DNA methylation levels at TF binding regions. CEBPA, HNF4A, ONECUT1, and FOXA1 share the same methylation patterns, while CTCF's differ. These patterns characterize alternative functions and chromatin landscapes of TF-bound regions. Leveraging our phylogenetic framework, we find DNA methylation gain upon evolutionary loss of TF occupancy, indicating coordinated evolution. Furthermore, each methylation pattern has its own evolutionary trajectory reflecting its genomic contexts. CONCLUSIONS: Our epigenomic analyses indicate a role for DNA methylation in TF binding changes across species including that specific DNA methylation profiles characterize TF binding and are associated with their regulatory activity, chromatin contexts, and evolutionary trajectories. | en_US |
dc.format.extent | 146 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Genome Biol | en_US |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Reprints and permissions | |
dc.subject | DNA methylation | en_US |
dc.subject | Evolution | en_US |
dc.subject | Mammals | en_US |
dc.subject | Transcription factor binding | en_US |
dc.subject | Animals | en_US |
dc.subject | DNA Methylation | en_US |
dc.subject | Binding Sites | en_US |
dc.subject | Humans | en_US |
dc.subject | Transcription Factors | en_US |
dc.subject | Evolution, Molecular | en_US |
dc.subject | Mice | en_US |
dc.subject | Rats | en_US |
dc.subject | CpG Islands | en_US |
dc.subject | Dogs | en_US |
dc.subject | Hepatocyte Nuclear Factor 3-alpha | en_US |
dc.subject | Protein Binding | en_US |
dc.subject | Liver | en_US |
dc.subject | Hepatocyte Nuclear Factor 4 | en_US |
dc.subject | CCAAT-Enhancer-Binding Proteins | en_US |
dc.title | DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contexts. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s) 2024. | |
dc.identifier.doi | 10.1186/s13059-024-03218-6 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38844976 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 25 | en_US |
dcterms.dateAccepted | 2024-03-15 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |