Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning
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Abstract
The relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.
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In Drosophila, pronounced changes in enhancer activity during embryonic development seem to occur without prominent changes in their 3D conformation.
“In Drosophila, pronounced changes in enhancer activity during embryonic development seem to occur without prominent changes in their 3D conformation [392, 393].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [393]
Neither Hi-C nor Micro-C detected a widespread enrichment for enhancer-promoter interactions in early Drosophila embryos irrespective of the activity of these elements.
“For example, neither Hi-C nor Micro-C detected a widespread enrichment for enhancer–promoter interactions in early Drosophila embryos irrespective of the activity of these elements [393].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [393]
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- Authors
- Ing-Simmons, E., Vaid, R., Bing, X. Y., Levine, M., Mannervik, M., & Vaquerizas, J. M.
- Affiliations
- Stockholm University (SE)
- Princeton University (US)
- Max Planck Institute for Molecular Biomedicine (DE)
- Corresponding author
- Vaquerizas, Juan M.
- Venue
- Nature Genetics
- Published
- 2021-04
- Volume
- 53
- Issue
- 4
- Pages
- 487-499
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC8035076
- OpenAlex
- W3145419749
- Cited by
- 159
- References
- 158
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 24 · 2023: 27 · 2022: 41 · 2021: 30 · 2020: 2 · 2012: 1
- FWCI
- 10.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Academy of Medical Sciences (APR3∖1017)
- European Commission (HORIZON2020, 643062)
- Deutsche Forschungsgemeinschaft (CRU326, VA 1456/1, 422857230, SPP2202, 329621271)
- Cancerfonden
- Karolinska Institutet
- Max-Planck-Gesellschaft
- Vetenskapsrådet
- National Institutes of Health (CRU326)
- Medical Research Council (MC_UP_1605/10)
- National Institute of General Medical Sciences (R35GM118147)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin conformation, gene expression regulation, dorsoventral patterning, Drosophila melanogaster embryo, enhancers, tissue-specific gene expression, chromatin organization, single-cell RNA sequencing, chromatin domains
- MeSH terms
- Animals, Cell Differentiation, Chromatin, Drosophila melanogaster, Embryo, Nonmammalian, Enhancer Elements, Genetic, Female, Histones, Male, Organ Specificity, Promoter Regions, Genetic, Transcription, Genetic, Genome, Gene Expression Regulation, Developmental, Cell Lineage, Body Patterning, Drosophila Proteins, Animals, Genetically Modified, Single-Cell Analysis, High-Throughput Nucleotide Sequencing
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