Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development
Open accessAbstract
Enhancers are distal regulatory elements that can activate tissue-specific gene expression and are abundant throughout mammalian genomes. Although substantial progress has been made toward genome-wide annotation of mammalian enhancers, their temporal activity patterns and global contributions in the context of developmental in vivo processes remain poorly explored. Here we used epigenomic profiling for H3K27ac, a mark of active enhancers, coupled to transgenic mouse assays to examine the genome-wide utilization of enhancers in three different mouse tissues across seven developmental stages. The majority of the ∼90,000 enhancers identified exhibited tightly temporally restricted predicted activity windows and were associated with stage-specific biological functions and regulatory pathways in individual tissues. Comparative genomic analysis revealed that evolutionary conservation of enhancers decreases following midgestation across all tissues examined. The dynamic enhancer activities uncovered in this study illuminate rapid and pervasive temporal in vivo changes in enhancer usage that underlie processes central to development and disease.
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This supports a gene regulatory model with more dynamic chromatin accessibility at distal regulatory elements compared to promoters.
“supporting a gene regulatory model with more dynamic chromatin accessibility at distal regulatory elements compared to promoters18.”
From Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens (2021) · cites this paper as [18]
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- Authors
- Nord, A. S., Blow, M. J., Attanasio, C., Akiyama, J. A., Holt, A., Hosseini, R., Phouanenavong, S., Plajzer-Frick, I., Shoukry, M., Afzal, V., Rubenstein, J. L. R., Rubin, E. M., Pennacchio, L. A., & Visel, A.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- University of California, San Francisco (US)
- Corresponding author
- Pennacchio, Len A.
- Visel, Axel
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 155
- Issue
- 7
- Pages
- 1521-1531
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3989111
- OpenAlex
- W2041171293
- Cited by
- 375
- References
- 83
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 24 · 2023: 26 · 2022: 18 · 2021: 33 · 2020: 38 · 2019: 41 · 2018: 27 · 2017: 26 · 2016: 38 · 2015: 40 · 2014: 22
- FWCI
- 14.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- National Institute of Mental Health (R37MH049428, R01MH081880)
- National Human Genome Research Institute (R01HG003988)
- National Institute of General Medical Sciences (GM105202, F32GM105202)
- National Institute of Neurological Disorders and Stroke (R01NS062859, R01 NS062859A, R01NS034661, R01NS099099)
- National Institute of Dental and Craniofacial Research (U01DE020060)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- enhancers, enhancer activity, mammalian development, H3K27ac, tissue-specific gene expression, developmental stages, enhancer evolution, enhancer conservation, epigenomics
- MeSH terms
- Acetylation, Animals, Enhancer Elements, Genetic, Histones, Mice, Transgenic, Organ Specificity, Gene Expression Regulation, Developmental, Evolution, Molecular, Epigenesis, Genetic, Mice, Genome-Wide Association Study
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