Pagni, Susanna;
Custodio, Helena Martins;
Frankish, Adam;
Mudge, Jonathan M;
Mills, James D;
Sisodiya, Sanjay M;
(2023)
SCN1A: bioinformatically-informed revised boundaries for promoter and enhancer regions.
Human Molecular Genetics
, Article ddad015. 10.1093/hmg/ddad015.
(In press).
Preview |
Text
SCN1A - bioinformatically-informed revised boundaries for promoter and enhancer regions.pdf Download (1MB) | Preview |
Abstract
Pathogenic variations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene are responsible for multiple epilepsy phenotypes, including Dravet syndrome (DS), febrile seizures (FS), and genetic epilepsy with febrile seizures plus (GEFS+). Phenotypic heterogeneity is a hallmark of SCN1A-related epilepsies, the causes of which are yet to be clarified. Genetic variation in the non-coding regulatory regions of SCN1A could be one potential causal factor. However, a comprehensive understanding of the SCN1A regulatory landscape is currently lacking. Here, we summarised the current state of knowledge of SCN1A regulation, providing details of its promoter and enhancer regions. We then integrated currently available data on SCN1A promoters by extracting information related to the SCN1A locus from genome-wide repositories, and clearly defined the promoter and enhancer regions of SCN1A. Further, we explored the cellular specificity of differential SCN1A promoter usage. We also reviewed and integrated the available human brain-derived enhancer databases and mouse-derived data to provide a comprehensive computationally-developed summary of SCN1A brain-active enhancers. By querying genome-wide data repositories, extracting SCN1A-specific data and integrating the different types of independent evidence, we created a comprehensive catalogue that better defines the regulatory landscape of SCN1A, which could be used to explore the role of SCN1A regulatory regions in disease.
| Type: | Article |
|---|---|
| Title: | SCN1A: bioinformatically-informed revised boundaries for promoter and enhancer regions |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/hmg/ddad015 |
| Publisher version: | https://doi.org/10.1093/hmg/ddad015 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2023. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10165043 |
Archive Staff Only
 |
View Item |
