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Cited by 97Genomics and Chromatin DynamicsEpigenetics and DNA MethylationPluripotent Stem Cells Research

The chromatin, topological and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo

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Crispatzu, Giuliano, Rehimi, Rizwan, Pachano, Tomas, Bleckwehl, Tore, Cruz-Molina, Sara, Xiao, Cally, Mahabir, Esther, Bazzi, Hisham +1 more·2021·Nature Communications
DOI 10.1038/s41467-021-24641-4PMC PMC8285398

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Abstract

Poised enhancers (PEs) represent a genetically distinct set of distal regulatory elements that control the expression of major developmental genes. Before becoming activated in differentiating cells, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally characterized in embryonic stem cells (ESC), it is currently unknown whether PEs are functionally conserved in vivo. Here, we show that the chromatin and 3D structural features of PEs are conserved among mouse pluripotent cells both in vitro and in vivo. We also uncovered that the interactions between PEs and their target genes are globally controlled by the combined action of Polycomb, Trithorax and architectural proteins. Moreover, distal regulatory sequences located close to developmental genes and displaying the typical genetic ( i.e . CpG islands) and chromatin ( i.e . high accessibility and H3K27me3 levels) features of PEs are commonly found across vertebrates. These putative PEs show high sequence conservation within specific vertebrate clades, with only a few being evolutionary conserved across all vertebrates. Lastly, by genetically disrupting PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential roles during the induction of major developmental genes in vivo.

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  • Many developmental enhancers are found in the poised or Polycomb-repressed state in early development.

    “Many developmental enhancers are found in the poised or Polycomb-repressed state in early development [139, 142, 143], and the functional role of these states remains an area of active research.”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [142]

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Cited by

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Authors
Crispatzu, G., Rehimi, R., Pachano, T., Bleckwehl, T., Cruz-Molina, S., Xiao, C., Mahabir, E., Bazzi, H., & Rada-Iglesias, A.
Affiliations
  • University of Cologne (DE)
  • Max Planck Institute for Molecular Biomedicine (DE)
  • University of Southern California (US)
Corresponding author
Crispatzu, Giuliano
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-07-16
Volume
12
Issue
1
Pages
4344-4344
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-24641-4
PMC
PMC8285398
OpenAlex
W3177893949
Cited by
97
References
14
Citations by year
2026: 14 · 2025: 25 · 2024: 15 · 2023: 19 · 2022: 20 · 2021: 4
FWCI
4.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministerio de Ciencia, Innovación y Universidades (PGC 2018)
  • Deutsche Forschungsgemeinschaft (SFB829, CRU 329, 386793560, 73111208)
  • Universität zu Köln
  • H2020 European Research Council (862022)
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 › Pluripotent Stem Cells Research
Keywords
poised enhancers, pluripotency, chromatin accessibility, 3D genome organization, Polycomb, trithorax, architectural proteins, H3K27me3, CpG islands, developmental gene regulation, enhancer evolution, sequence conservation, embryonic stem cells, mouse embryo, chick embryo, enhancer disruption
MeSH terms
Chromatin Immunoprecipitation Sequencing, Animals, Cell Differentiation, Cell Line, Chick Embryo, Chromatin, Enhancer Elements, Genetic, Germ Layers, Histones, Homozygote, Phylogeny, Transcription Factors, Gene Deletion, Gene Expression Regulation, Developmental, CpG Islands, Epigenesis, Genetic, Mice, Embryonic Stem Cells, Polycomb-Group Proteins

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