Methyl-CpG-binding protein 2 (MeCP2) is a master regulator of neuronal gene expression, and its genetic mutations cause the neurodevelopmental disorder Rett syndrome. Single-molecule experiments have enabled the direct visualization of the dynamics of MeCP2 on DNA, shedding light on how the specific chromatin context tunes MeCP2 function.
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References
Lewis, J. D. et al. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69, 905–914 (1992). This paper reports the detection of MeCP2 in nuclear extracts and its methyl-CpG binding activity.
Amir, R. E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185–188 (1999). This paper reports the first mutations of the MECP2 gene, located on the X chromosome, as the cause of RTT.
Lombardi, L. M., Baker, S. A. & Zoghbi, H. Y. MECP2 disorders: from the clinic to mice and back. J. Clin. Invest. 125, 2914–2923 (2015). A review article that presents the molecular function of MeCP2, the clinical profiles of RTT and MECP2 duplication syndrome and therapeutic strategies for these disorders.
Connolly, D. R. & Zhou, Z. Genomic insights into MeCP2 function: a role for the maintenance of chromatin architecture. Curr. Opin. Neurobiol. 59, 174–179 (2019). A review article that presents MeCP2’s context-specific gene regulatory functions and proposes a model in which MeCP2 serves as a global organizer of chromatin architecture.
Chua, G. N. L. & Liu, S. When force met fluorescence: single-molecule manipulation and visualization of protein-DNA interactions. Annu. Rev. Biophys. 53, 169–191 (2024). A review article that presents single-molecule correlative force and fluorescence microscopy and its use in imaging protein dynamics on DNA and chromatin.
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This is a summary of: Chua, G. N. L. et al. Differential dynamics specify MeCP2 function at nucleosomes and methylated DNA. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-024-01373-9 (2024).
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Dynamics of an epigenetic regulator on chromatin observed at the single-molecule level. Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01374-8
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DOI: https://doi.org/10.1038/s41594-024-01374-8
