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A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics

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Abstract
Myocyte enhancer factor 2C (MEF2C) is a core transcription factor in neurodevelopment and aberrations are typically associated with a Rett-like syndrome, featured by severe intellectual disability, seizures and stereotypic movements. However, structural variants upstream of MEF2C have been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements represents the underlying genetic cause in these cases. To shed light on how these aberrations impact MEF2C regulation, we dissected the MEF2C regulatory landscape. Using Circularized Chromosome Conformation Capture (4C) sequencing in a neuronal cell line, we revealed a complex interaction network in which the MEF2C promoter physically contacts several distal enhancers located upstream of the coding sequence. Luciferase reporter assays confirmed enhancer activity for thirteen out of sixteen selected candidate enhancers. Moreover, using enhancer assays in zebrafish, we characterized eight enhancers with in vivo neuronal activity. While each of these enhancers displayed a distinct activity pattern, several showed overlapping activity in the forebrain, notochord or neurons above the eye. In summary, we disentangled a complex regulatory network governing neuronal MEF2C transcription that involves multiple distal enhancers. Disrupting this regulatory structure is likely detrimental to normal neurodevelopment and can give rise to neurodevelopmental disorders such as Rett-like syndrome.

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MLA
D’haene, Eva, et al. “A Neuronal Enhancer Network Upstream of MEF2C Is Compromised in Patients with Rett-like Characteristics.” Epigenetics in the Nervous System : Development and Disease, Conference Abstracts, 2018.
APA
D’haene, E., Bar-Yaacov, R., Bariah, I., Vantomme, L., Van Loo, S., Avila Cobos, F., … Vergult, S. (2018). A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics. Epigenetics in the Nervous System : Development and Disease, Conference Abstracts. Presented at the Epigenetics in the Nervous System : Development and Disease, Stockholm, Sweden.
Chicago author-date
D’haene, Eva, Reut Bar-Yaacov, Inbar Bariah, Lies Vantomme, Sien Van Loo, Francisco Avila Cobos, Karen Verboom, et al. 2018. “A Neuronal Enhancer Network Upstream of MEF2C Is Compromised in Patients with Rett-like Characteristics.” In Epigenetics in the Nervous System : Development and Disease, Conference Abstracts.
Chicago author-date (all authors)
D’haene, Eva, Reut Bar-Yaacov, Inbar Bariah, Lies Vantomme, Sien Van Loo, Francisco Avila Cobos, Karen Verboom, Reut Eshel, Rawan Alatawna, Björn Menten, Ramon Birnbaum, and Sarah Vergult. 2018. “A Neuronal Enhancer Network Upstream of MEF2C Is Compromised in Patients with Rett-like Characteristics.” In Epigenetics in the Nervous System : Development and Disease, Conference Abstracts.
Vancouver
1.
D’haene E, Bar-Yaacov R, Bariah I, Vantomme L, Van Loo S, Avila Cobos F, et al. A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics. In: Epigenetics in the Nervous System : Development and Disease, Conference abstracts. 2018.
IEEE
[1]
E. D’haene et al., “A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics,” in Epigenetics in the Nervous System : Development and Disease, Conference abstracts, Stockholm, Sweden, 2018.
@inproceedings{8590878,
  abstract     = {{Myocyte enhancer factor 2C (MEF2C) is a core transcription factor in neurodevelopment and aberrations are typically associated with a Rett-like syndrome, featured by severe intellectual disability, seizures and stereotypic movements. However, structural variants upstream of MEF2C have been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements represents the underlying genetic cause in these cases. To shed light on how these aberrations impact MEF2C regulation, we dissected the MEF2C regulatory landscape.
Using Circularized Chromosome Conformation Capture (4C) sequencing in a neuronal cell line, we revealed a complex interaction network in which the MEF2C promoter physically contacts several distal enhancers located upstream of the coding sequence. Luciferase reporter assays confirmed enhancer activity for thirteen out of sixteen selected candidate enhancers. Moreover, using enhancer assays in zebrafish, we characterized eight enhancers with in vivo neuronal activity. While each of these enhancers displayed a distinct activity pattern, several showed overlapping activity in the forebrain, notochord or neurons above the eye.
In summary, we disentangled a complex regulatory network governing neuronal MEF2C transcription that involves multiple distal enhancers. Disrupting this regulatory structure is likely detrimental to normal neurodevelopment and can give rise to neurodevelopmental disorders such as Rett-like syndrome.}},
  author       = {{D'haene, Eva and Bar-Yaacov, Reut and Bariah, Inbar and Vantomme, Lies and Van Loo, Sien and Avila Cobos, Francisco and Verboom, Karen and Eshel, Reut and Alatawna, Rawan and Menten, Björn and Birnbaum, Ramon and Vergult, Sarah}},
  booktitle    = {{Epigenetics in the Nervous System : Development and Disease, Conference abstracts}},
  language     = {{eng}},
  location     = {{Stockholm, Sweden}},
  title        = {{A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics}},
  year         = {{2018}},
}