ArticleHuman molecular genetics2018
Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Case Report: Influenza B-triggered CIDP revealing PMP22-related Dejerine-Sottas-like neuropathy in a child-biphasic cytokine dynamics and response to immunotherapy.Frontiers in medicine · 2026Article
- PMP2 Enhances Schwann Cell Metabolism and Promotes Myelination.Journal of neurochemistry · 2025Article
- Article
- Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Review
- Three-dimensional genome structure and function.MedComm · 2023Review
- Review
- CMT1A current gene therapy approaches and promising biomarkers.Neural regeneration research · 2023Review
- Novel gene-intergenic fusion involving ubiquitin E3 ligase UBE3C causes distal hereditary motor neuropathy.Brain : a journal of neurology · 2023Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies.International journal of molecular sciences · 2021Review
- A Comprehensive Analysis of SE-lncRNA/mRNA Differential Expression Profiles During Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2021Article
- Direct relationship between increased expression and mistrafficking of the Charcot-Marie-Tooth-associated protein PMP22.The Journal of biological chemistry · 2020Article
- Gene Therapy Options as New Treatment for Inherited Peripheral Neuropathy.Experimental neurobiology · 2020Review
- Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves.Human molecular genetics · 2020Article
- Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice.Nucleic acids research · 2020Article
- Regulating PMP22 expression as a dosage sensitive neuropathy gene.Brain research · 2020Review
- Dissecting Tissue-Specific Super-Enhancers by Integrating Genome-Wide Analyses and CRISPR/Cas9 Genome Editing.Journal of mammary gland biology and neoplasia · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype. Recently we identified a potential super-enhancer approximately 90-130 kb upstream of the Pmp22 transcription start sites. This super-enhancer encompasses a cluster of individual enhancers that have the acetylated histone H3K27 active enhancer mark, and coincides with smaller duplications identified in patients with milder CMT1A-like symptoms, where the PMP22 coding region itself was not part of the duplication. In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression.
Indexed as
Identifiers
What OpenQuestion holds
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.