ArticleBMC genomics2018
Dichotomy in redundant enhancers points to presence of initiators of gene regulation.
Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Mechanisms of robustness in gene regulatory networks involved in neural development.Frontiers in molecular neuroscience · 2023Review
- Transcriptional enhancers and their communication with gene promoters.Cellular and molecular life sciences : CMLS · 2021Review
- Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers.Cell reports · 2020Article
- The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance.Genome biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe regulatory landscape of a gene locus often consists of several functionally redundant enhancers establishing phenotypic robustness and evolutionary stability of its regulatory program. However, it is unclear what mechanisms are employed by redundant enhancers to cooperatively orchestrate gene expression.
resultsBy comparing redundant enhancers to single enhancers (enhancers present in a single copy in a gene locus), we observed that the DNA sequence encryption differs between these two classes of enhancers, suggesting a difference in their regulatory mechanisms. Initiator enhancers, which are a subset of redundant enhancers and show similar sequence encryption to single enhancers, differ from the rest of redundant enhancers in their sequence encryption, evolutionary conservation and proximity to target genes. Genes hosting initiator enhancers in their loci feature elevated levels of expression. Initiator enhancers show a high level of 3D chromatin contacts with both transcription start sites and regular enhancers, suggesting their roles as primary activators and intermediate catalysts of gene expression, through which the regulatory signals of redundant enhancers are propagated to the target genes. In addition, GWAS and eQTLs variants are significantly enriched in initiator enhancers compared to redundant enhancers, suggesting a key functional role these sequences play in gene regulation.
conclusionsThe specific characteristics and widespread abundance of initiator enhancers advocate for a possible universal hierarchical mechanism of tissue-specific gene regulation involving multiple redundant enhancers acting through initiator enhancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.