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Cited by 945Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationChromosomal and Genetic Variations

Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution

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Long, Hannah K., Prescott, Sara L., Wysocka, Joanna·2016·Cell
DOI 10.1016/j.cell.2016.09.018PMC PMC5123704
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Abstract

A class of cis-regulatory elements, called enhancers, play a central role in orchestrating spatiotemporally precise gene-expression programs during development. Consequently, divergence in enhancer sequence and activity is thought to be an important mediator of inter- and intra-species phenotypic variation. Here, we give an overview of emerging principles of enhancer function, current models of enhancer architecture, genomic substrates from which enhancers emerge during evolution, and the influence of three-dimensional genome organization on long-range gene regulation. We discuss intricate relationships between distinct elements within complex regulatory landscapes and consider their potential impact on specificity and robustness of transcriptional regulation.

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  • The prevalence of flexible enhancer organisation is supported by rapid evolutionary turnover of enhancers, which exceeds that of proximal promoter regions.

    “The prevalence of flexible enhancer organisation is also supported by rapid evolutionary turnover of enhancers, which exceeds that of proximal promoter regions [29, 99, 100].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [29]

    Section I, “General principles of enhancer function” (page unavailable), describes high rates of enhancer turnover and links compensatory motif turnover to flexible enhancer organisation. The passages do not compare enhancer turnover with turnover in proximal promoter regions, so the claimed difference in rates is not supported by this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Proposed models for enhancer grammar range from very rigid to flexible, largely dependent on the species, cell types and loci in which they were formulated.

    “The various proposed models for enhancer grammar range from very rigid to flexible, largely dependent on the species, cell types and loci in which they were formulated (reviewed in [29]).”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [29]

    In the Introduction, under “Motif organization, enhancer grammar and models of enhancer architecture” (page unavailable), the review contrasts the rigid enhanceosome model with the more flexible billboard model and describes a spectrum between them. It gives examples from particular species and loci, but does not establish that the differences among proposed models are largely dependent on the species, cell types, and loci in which they were formulated. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • At the DNA level, enhancers represent clusters of binding sites for sequence-specific transcription factors.

    “At the DNA level, enhancers represent clusters of binding sites for sequence-specific transcription factors (TFs) (Fig. 1A) (reviewed in [29, 30]).”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [29]

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Authors
Long, H. K., Prescott, S. L., & Wysocka, J.
Affiliations
  • Stanford Medicine (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Wysocka, Joanna
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2016-11
Volume
167
Issue
5
Pages
1170-1187
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2016.09.018
PMC
PMC5123704
OpenAlex
W2556513628
Cited by
945
References
30
Citations by year
2026: 78 · 2025: 90 · 2024: 103 · 2023: 114 · 2022: 97 · 2021: 112 · 2020: 126 · 2019: 94 · 2018: 90 · 2017: 38 · 2012: 1
FWCI
6.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • Wellcome Trust (106051/Z/14/Z)
  • National Institute of General Medical Sciences (R01GM112720)
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 › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
enhancers, cis-regulatory elements, enhancer evolution, developmental gene regulation, enhancer architecture, 3D genome organization, long-range gene regulation, phenotypic variability
MeSH terms
Blood, Blood Cells, Enhancer Elements, Genetic, Hematopoiesis, Humans, Transcription, Genetic, Evolution, Molecular, Quantitative Trait Loci, Genome-Wide Association Study, Epigenomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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