The Chromatin Structure at the MECP2 Gene and In Silico Prediction of Potential Coding and Non-Coding MECP2 Splice Variants.
Danilo ShevkoplyasYen My VuuJames R DavieMojgan RastegarPublished in: International journal of molecular sciences (2022)
Methyl CpG binding protein 2 (MeCP2) is an epigenetic reader that binds to methylated CpG dinucleotides and regulates gene transcription. Mecp2 / MECP2 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 MECP2 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 MECP2 gene and its cis -regulatory elements. We conclude that the human MECP2 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).
Keyphrases
- dna methylation
- genome wide
- copy number
- gene expression
- transcription factor
- binding protein
- endothelial cells
- small molecule
- multiple sclerosis
- white matter
- oxidative stress
- risk assessment
- machine learning
- molecular docking
- climate change
- single cell
- big data
- functional connectivity
- brain injury
- electronic health record
- protein protein
- subarachnoid hemorrhage
- cerebral ischemia