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Open AccessArticle

In Silico Study of Rett Syndrome Treatment-Related Genes, MECP2, CDKL5, and FOXG1, by Evolutionary Classification and Disordered Region Assessment

1
Advanced Life Sciences Program, Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
2
Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
3
Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5593; https://doi.org/10.3390/ijms20225593
Received: 30 September 2019 / Revised: 31 October 2019 / Accepted: 5 November 2019 / Published: 8 November 2019
Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which has multiple functions such as binding to methylated DNA or interacting with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We investigated the evolution and molecular features of MeCP2, CDKL5, and FOXG1 and their binding partners using phylogenetic profiling to gain a better understanding of their similarities. We also predicted the structural order–disorder propensity and assessed the evolutionary rates per site of MeCP2, CDKL5, and FOXG1 to investigate the relationships between disordered structure and other related properties with RTT. Here, we provide insight to the structural characteristics, evolution and interaction landscapes of those three proteins. We also uncovered the disordered structure properties and evolution of those proteins which may provide valuable information for the development of therapeutic strategies of RTT. View Full-Text
Keywords: Rett syndrome; intrinsically disordered region; phylogenetic profile analysis; post-transcriptional modification; methyl-CpG-binding protein 2; cyclin-dependent kinase-like 5; forkhead box protein G1 Rett syndrome; intrinsically disordered region; phylogenetic profile analysis; post-transcriptional modification; methyl-CpG-binding protein 2; cyclin-dependent kinase-like 5; forkhead box protein G1
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Fahmi, M.; Yasui, G.; Seki, K.; Katayama, S.; Kaneko-Kawano, T.; Inazu, T.; Kubota, Y.; Ito, M. In Silico Study of Rett Syndrome Treatment-Related Genes, MECP2, CDKL5, and FOXG1, by Evolutionary Classification and Disordered Region Assessment. Int. J. Mol. Sci. 2019, 20, 5593.

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