Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development
Abstract
Chromatin modifications are associated with many aspects of gene expression, yet their role in cellular transitions during development remains elusive. Here, we use a new approach to obtain cell type-specific information on chromatin state and RNA polymerase II (Pol II) occupancy within the multicellular Drosophila melanogaster embryo. We directly assessed the relationship between chromatin modifications and the spatio-temporal activity of enhancers. Rather than having a unique chromatin state, active developmental enhancers show heterogeneous histone modifications and Pol II occupancy. Despite this complexity, combined chromatin signatures and Pol II presence are sufficient to predict enhancer activity de novo. Pol II recruitment is highly predictive of the timing of enhancer activity and seems dependent on the timing and location of transcription factor binding. Chromatin modifications typically demarcate large regulatory regions encompassing multiple enhancers, whereas local changes in nucleosome positioning and Pol II occupancy delineate single active enhancers. This cell type-specific view identifies dynamic enhancer usage, an essential step in deciphering developmental networks.
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H3K4me1, associated with the binding of Trithorax/MLL complexes, is taken to be the hallmark of both primed and active enhancers, whilst active enhancers additionally tend to associate with H3K27ac.
“Currently mono-methylation of histone H3 lysine 4 (H3K4me1), associated with the binding of Trithorax/MLL complexes, is taken to be the hallmark of both ‘primed’ and active enhancers, whilst active enhancers additionally tend to associate with the acetylation of histone H3 lysine 27 (H3K27ac) [133–137].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [137]
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“Therefore, the local distribution of chromatin modifications around transcription factor binding sites rather than the simple presence or absence of these marks may better reflect enhancer activity, with a bimodal distribution being indicative of an active enhancer, whereas a single peak indicates a switch to an inact…”
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Self-citation
- Authors
- Bonn, S., Zinzen, R. P., Girardot, C., Gustafson, E. H., Perez-Gonzalez, A., Delhomme, N., Ghavi-Helm, Y., Wilczyński, B., Riddell, A., & Furlong, E. E. M.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Furlong, Eileen E M
- ORCID
- Venue
- Nature Genetics
- Published
- 2012-01-08
- Volume
- 44
- Issue
- 2
- Pages
- 148-156
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2019005509
- Cited by
- 502
- References
- 10
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 15 · 2023: 22 · 2022: 26 · 2021: 34 · 2020: 49 · 2019: 33 · 2018: 41 · 2017: 37 · 2016: 52 · 2015: 51 · 2014: 49 · 2013: 36 · 2012: 35
- FWCI
- 22.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- enhancer activity, chromatin state, histone modifications, RNA polymerase II occupancy, Drosophila melanogaster embryo, mesoderm, embryonic development, transcription factor binding, nucleosome positioning, enhancer dynamics, cell type-specific chromatin
- MeSH terms
- Animals, Chromatin, Drosophila melanogaster, Enhancer Elements, Genetic, Histones, RNA Polymerase II, Transcription Factors, Gene Expression Regulation, Developmental, Embryonic Development, Chromatin Immunoprecipitation
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