The Chromatin Structure at the MECP2 Gene and In Silico Prediction of Potential Coding and Non-Coding MECP2 Splice Variants

• Published in: International journal of molecular sciences Vol. 23; no. 24; p. 15643
• Main Authors: Shevkoplyas, Danilo, Vuu, Yen My, Davie, James R, Rastegar, Mojgan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.12.2022; MDPI
• Subjects: Alternative splicing; Ataxia; Binding sites; Brain; Chromatin; Chromatin - genetics; CpG islands; Deoxyribonucleic acid; DNA; DNA methylation; Domains; Enzymes; Epigenetics; Exons; Female; Frontal gyrus; Gene expression; Genomes; genomics; Histones; Histones - genetics; Humans; Isoforms; Male; MeCP2 isoforms; MeCP2 protein; Methyl-CpG binding protein; Methyl-CpG-Binding Protein 2 - genetics; Methyl-CpG-Binding Protein 2 - metabolism; Mutation; Neurodevelopment; Neurodevelopmental disorders; Post-translation; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Regulatory sequences; Rett syndrome; Rett Syndrome - genetics; Rett Syndrome - metabolism; RTT; UCSC; RTT; alternative splicing; UCSC; genomics; MeCP2 isoforms; ATAC-seq; epigenetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232415643

Methyl CpG binding protein 2 (MeCP2) is an epigenetic reader that binds to methylated CpG dinucleotides and regulates gene transcription. / gene has 4 exons, encoding for protein isoforms MeCP2E1 and MeCP2E2. MeCP2 plays key roles in neurodevelopment, therefore, its gain- and loss-of-function mutations lead to neurodevelopmental disorders including Rett Syndrome. Here, we describe the structure, functional domains, and evidence support for potential additional alternatively spliced transcripts and protein isoforms. We conclude that NCBI MeCP2 isoforms 3 and 4 contain certain MeCP2 functional domains. Our in silico analysis led to identification of histone modification and accessibility profiles at the gene and its -regulatory elements. We conclude that the human gene associated histone post-translational modifications exhibit high similarity between males and females. Between brain regions, histone modifications were found to be less conserved and enriched within larger genomic segments named as "S1-S11". We also identified highly conserved DNA accessibility regions in different tissues and brain regions, named as "A1-A9" and "B1-B9". DNA methylation profile was similar between mid-frontal gyrus of donors 35 days-25 years of age. Based on ATAC-seq data, the identified hypomethylated regions "H1-H8" intersected with most regions of the accessible chromatin (A regions).