Epigenetic priming of mammalian embryonic enhancer elements coordinates developmental gene networks Article Swipe
Christopher D Todd
,
Jannat Ijaz
,
Fereshteh Torabi
,
Oleksandr Dovgusha
,
Steve Bevan
,
Olivia Cracknell
,
Tim Lohoff
,
Stephen J. Clark
,
Ricard Argelaguet
,
Joshua L. Pierce
,
Ioannis Kafetzopoulos
,
Alice Santambrogio
,
Jennifer Nichols
,
Ferdinand von Meyenn
,
Ufuk Günesdogan
,
Stefan Schoenfelder
,
Wolf Reik
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-025-03658-8
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-025-03658-8
Background Embryonic development requires the accurate spatiotemporal execution of cell lineage-specific gene expression programs, which are controlled by transcriptional enhancers. Developmental enhancers adopt a primed chromatin state prior to their activation. How this primed enhancer state is established and maintained and how it affects the regulation of developmental gene networks remains poorly understood. Results Here, we use comparative multi-omic analyses of human and mouse early embryonic development to identify subsets of postgastrulation lineage-specific enhancers which are epigenetically primed ahead of their activation, marked by the histone modification H3K4me1 within the epiblast. We show that epigenetic priming occurs at lineage-specific enhancers for all three germ layers and that epigenetic priming of enhancers confers lineage-specific regulation of key developmental gene networks. Surprisingly in some cases, lineage-specific enhancers are epigenetically marked already in the zygote, weeks before their activation during lineage specification. Moreover, we outline a generalizable strategy to use naturally occurring human genetic variation to delineate important sequence determinants of primed enhancer function. Conclusions Our findings identify an evolutionarily conserved program of enhancer priming and begin to dissect the temporal dynamics and mechanisms of its establishment and maintenance during early mammalian development.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s13059-025-03658-8
- OA Status
- gold
- Cited By
- 3
- References
- 82
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412522182
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412522182Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1186/s13059-025-03658-8Digital Object Identifier
- Title
-
Epigenetic priming of mammalian embryonic enhancer elements coordinates developmental gene networksWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-07-18Full publication date if available
- Authors
-
Christopher D Todd, Jannat Ijaz, Fereshteh Torabi, Oleksandr Dovgusha, Steve Bevan, Olivia Cracknell, Tim Lohoff, Stephen J. Clark, Ricard Argelaguet, Joshua L. Pierce, Ioannis Kafetzopoulos, Alice Santambrogio, Jennifer Nichols, Ferdinand von Meyenn, Ufuk Günesdogan, Stefan Schoenfelder, Wolf ReikList of authors in order
- Landing page
-
https://doi.org/10.1186/s13059-025-03658-8Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1186/s13059-025-03658-8Direct OA link when available
- Concepts
-
Enhancer, Biology, Epigenetics, Chromatin, Genetics, Lineage (genetic), Histone, Regulation of gene expression, Gene, Enhancer RNAs, Cell biology, Evolutionary biology, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
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2025: 3Per-year citation counts (last 5 years)
- References (count)
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82Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| cited_by_percentile_year.min | 96 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 17 |
| citation_normalized_percentile.value | 0.94396357 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |