Abstract
Rett Syndrome affects about one in every 10,000 to 15,000 births. It is a genetic neurodevelopmental disorder that mainly occurs in females. Affected males die in infancy because the syndrome exhibits an X‐linked dominant pattern of inheritance. Rett Syndrome is caused by mutations in the X‐linked Methyl CpG binding protein 2 (MeCP2) coding gene. MeCP2 is necessary for epigenetic regulation of gene expression. This protein represses transcription by acting as a molecular bridge between methylated DNA and a complex of co‐repressor proteins including histone deacetylases and Sin3A. Mutations of MeCP2 cause overexpression of several genes during brain development. MeCP2 is a 52‐kDa protein with two functional domains: the transcriptional repressor domain (TRD) and the methyl‐CpG binding domain (MBD). Four notable amino acids found within the MBD are Arg106, Arg133, Phe155, and Thr158. Mutations at these four locations result in a decreased binding affinity of MeCP2 to methylated DNA: 2‐fold for mutated Thr158 and 100‐fold for the remaining mutated amino acids. The MBD has three beta sheets with Thr158 located on the c‐terminal end. Here, hydrophilic residues interact specifically with the methylated DNA. The Hartford Union High School SMART (Students Modeling A Research Topic) Team designed a model of MeCP2 using 3D printing technology to represent the MBD‐methylated DNA complex. The model highlights the amino acids involved in the interaction between MeCP2 and methylated DNA. Modeling the structure of MeCP2 allows for a more detailed understanding of the interaction between MeCP2 and DNA. This information will be crucial for designing treatments or interventions to improve the quality of life for Rett syndrome patients.Support or Funding InformationThis work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
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