ArticlePLoS genetics2018
Cooperation, cis-interactions, versatility and evolutionary plasticity of multiple cis-acting elements underlie krox20 hindbrain regulation.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 22 citations in OpenAlex.
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- Sea lamprey enlightens the origin of the coupling of retinoic acid signaling to vertebrate hindbrain segmentation.Nature communications · 2024Article
- Three-dimensional genome structure and function.MedComm · 2023Review
- Shadow enhancers mediate trade-offs between transcriptional noise and fidelity.PLoS computational biology · 2023Article
- Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution.Nature communications · 2023Article
- Mechanisms of robustness in gene regulatory networks involved in neural development.Frontiers in molecular neuroscience · 2023Review
- OsTBP2.1, a TATA-Binding Protein, Alters the Ratio ofInternational journal of molecular sciences · 2022Article
- Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.Nature communications · 2021Article
- Enhancer redundancy in development and disease.Nature reviews. Genetics · 2021Review
- Dissecting cis-regulatory control of quantitative trait variation in a plant stem cell circuit.Nature plants · 2021Article
- Article
- Evolution of regulatory signatures in primate cortical neurons at cell-type resolution.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Positive autofeedback regulation ofGenes & development · 2020Article
- Sufficiency analysis of estrogen responsive enhancers using synthetic activators.Life science alliance · 2019Article
- Transcription factor autoregulation is required for acquisition and maintenance of neuronal identity.Development (Cambridge, England) · 2019Article
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Authors and funding
9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Cis-regulation plays an essential role in the control of gene expression, and is particularly complex and poorly understood for developmental genes, which are subject to multiple levels of modulation. In this study, we performed a global analysis of the cis-acting elements involved in the control of the zebrafish developmental gene krox20. krox20 encodes a transcription factor required for hindbrain segmentation and patterning, a morphogenetic process highly conserved during vertebrate evolution. Chromatin accessibility analysis reveals a cis-regulatory landscape that includes 6 elements participating in the control of initiation and autoregulatory aspects of krox20 hindbrain expression. Combining transgenic reporter analyses and CRISPR/Cas9-mediated mutagenesis, we assign precise functions to each of these 6 elements and provide a comprehensive view of krox20 cis-regulation. Three important features emerged. First, cooperation between multiple cis-elements plays a major role in the regulation. Cooperation can surprisingly combine synergy and redundancy, and is not restricted to transcriptional enhancer activity (for example, 4 distinct elements cooperate through different modes to maintain autoregulation). Second, several elements are unexpectedly versatile, which allows them to be involved in different aspects of control of gene expression. Third, comparative analysis of the elements and their activities in several vertebrate species reveals that this versatility is underlain by major plasticity across evolution, despite the high conservation of the gene expression pattern. These characteristics are likely to be of broad significance for developmental genes.
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