Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders
Copyright policy )Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders
Significance Loss-of-function mutations in MECP2 cause the neurological disorder Rett syndrome (RTT), but the precise molecular mechanism driving pathogenesis remains unclear. Using an unbiased approach to identify proteins that interact with MeCP2, we identified the transcription factor 20 (TCF20) complex and discovered that RTT-causing mutations in MECP2 disrupt this interaction. Using biochemical, morphological, behavioral, and transcriptional studies, we examined the importance of this interaction for brain function and found that the TCF20 complex plays a direct role in MeCP2-dependent gene regulation and modifies MECP2 -induced synaptic and behavioral deficits. Our data uncovered a previously unknown molecular aspect of MeCP2 function and revealed a converging molecular mechanism, whereby mutations of genes encoding several subunits in the same complex contribute to shared neurological symptoms.
- Essen University Hospital Germany
- Khalifa University of Science and Technology United Arab Emirates
- University of Alabama at Birmingham United States
- University of Tübingen Germany
- BAYLOR COLLEGE OF MEDICINE
Mice, Knockout, Neurons, Methyl-CpG-Binding Protein 2, Medizin, Brain, Nuclear Proteins, Mice, Transgenic, Biological Sciences, Models, Biological, Disease Models, Animal, Mice, Neurodevelopmental Disorders, Multiprotein Complexes, Mutation, Synapses, Animals, Disease Susceptibility, Alleles, Biomarkers, Protein Binding, Transcription Factors
Mice, Knockout, Neurons, Methyl-CpG-Binding Protein 2, Medizin, Brain, Nuclear Proteins, Mice, Transgenic, Biological Sciences, Models, Biological, Disease Models, Animal, Mice, Neurodevelopmental Disorders, Multiprotein Complexes, Mutation, Synapses, Animals, Disease Susceptibility, Alleles, Biomarkers, Protein Binding, Transcription Factors
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