ArticleHuman molecular genetics2019
A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
- Systematic assessment of structural variant annotation tools for genomic interpretation.Life science alliance · 2025Article
- Navigating an Uninformative Genomic Test Result: A Practical Guide.Journal of paediatrics and child health · 2025Review
- Identification and Copy Number Variant Analysis of Enhancer Regions of Genes Causing Spinocerebellar Ataxia.International journal of molecular sciences · 2024Article
- Chromosomal structural rearrangements implicate long non-coding RNAs in rare germline disorders.Human genetics · 2024Article
- Rare germline disorders implicate long non-coding RNAs disrupted by chromosomal structural rearrangements.medRxiv : the preprint server for health sciences · 2024Article
- The function ofFrontiers in cellular neuroscience · 2024Review
- Deciphering transcription factors and their corresponding regulatory elements during inhibitory interneuron differentiation using deep neural networks.Frontiers in cell and developmental biology · 2023Article
- The non-coding genome in genetic brain disorders: new targets for therapy?Essays in biochemistry · 2021Review
- Identification of neural oscillations and epileptiform changes in human brain organoids.Nature neuroscience · 2021Article
- Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms.American journal of human genetics · 2021Article
- Interpreting the impact of noncoding structural variation in neurodevelopmental disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Review
- Anxiolytic and Anxiogenic? How the Transcription Factor MEF2 Might Explain the Manifold Behavioral Effects of Oxytocin.Frontiers in endocrinology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, which do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. To characterize those elements that regulate MEF2C during neural development and that are affected by these SVs, we used genomic tools coupled with both in vitro and in vivo functional assays. Through circularized chromosome conformation capture sequencing (4C-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we revealed a complex interaction network in which the MEF2C promoter physically contacts several distal enhancers that are deleted or translocated by disease-associated SVs. A total of 16 selected candidate regulatory sequences were tested for enhancer activity in vitro, with 14 found to be functional enhancers. Further analyses of their in vivo activity in zebrafish showed that each of these enhancers has a distinct activity pattern during development, with eight enhancers displaying neuronal activity. In summary, our results disentangle a complex regulatory network governing neuronal MEF2C expression that involves multiple distal enhancers. In addition, the characterized neuronal enhancers pose as novel candidates to screen for mutations in neurodevelopmental disorders, such as Rett-like syndrome.
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