DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contexts Article Swipe
Martina Rimoldi
,
Ning Wang
,
Jilin Zhang
,
Diego Villar
,
Duncan T. Odom
,
Jussi Taipale
,
Paul Flicek
,
Maša Roller
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-024-03218-6
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-024-03218-6
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.
Related Topics
Concepts
DNA methylation
Biology
DNA binding site
Epigenomics
Genetics
Methylation
Epigenetics
RNA-Directed DNA Methylation
CTCF
Transcription factor
Chromatin
DNA
Computational biology
Gene
Promoter
Enhancer
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s13059-024-03218-6
- https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03218-6
- OA Status
- gold
- Cited By
- 21
- References
- 66
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399388201
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4399388201Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1186/s13059-024-03218-6Digital Object Identifier
- Title
-
DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contextsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-06Full publication date if available
- Authors
-
Martina Rimoldi, Ning Wang, Jilin Zhang, Diego Villar, Duncan T. Odom, Jussi Taipale, Paul Flicek, Maša RollerList of authors in order
- Landing page
-
https://doi.org/10.1186/s13059-024-03218-6Publisher landing page
- PDF URL
-
https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03218-6Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03218-6Direct OA link when available
- Concepts
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DNA methylation, Biology, DNA binding site, Epigenomics, Genetics, Methylation, Epigenetics, RNA-Directed DNA Methylation, CTCF, Transcription factor, Chromatin, DNA, Computational biology, Gene, Promoter, Enhancer, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
21Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 15, 2024: 3, 2023: 3Per-year citation counts (last 5 years)
- References (count)
-
66Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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