MeCP2, A Modulator of Neuronal Chromatin Organization Involved in Rett Syndrome

• Published in: Advances in experimental medicine and biology Vol. 978; pp. 3 - 21
• Main Authors: Martínez de Paz, Alexia, Ausió, Juan
• Format: Book Chapter Journal Article
• Language: English
• Published: Cham Springer International Publishing 2017
• Series: Advances in Experimental Medicine and Biology
• Subjects: Brain - metabolism; Brain - ultrastructure; Chromatin; Chromatin - metabolism; Chromatin - ultrastructure; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes, Human, X - genetics; CpG Islands - genetics; DNA Methylation; Epigenesis, Genetic - genetics; Genes, X-Linked; Histone Code - genetics; Histone Code - physiology; Histones - metabolism; Humans; MeCP2; Methyl-CpG-Binding Protein 2 - deficiency; Methyl-CpG-Binding Protein 2 - genetics; Methyl-CpG-Binding Protein 2 - physiology; Mutation; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurogenesis - genetics; Neurogenesis - physiology; Neurons - metabolism; Neurons - ultrastructure; Postmitotic neurons; Rett syndrome; Rett Syndrome - genetics; RNA - metabolism; DNA methylation; MeCP2; Chromatin; Postmitotic neurons; Rett syndrome
• ISBN: 9783319538884; 3319538888
• ISSN: 0065-2598; 2214-8019
• DOI: 10.1007/978-3-319-53889-1_1

From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners. The final outcome is a highly specialized chromatin organization wherein linker histones (histones of the H1 family) and MeCP2 share an organizational role that dynamically changes during neuronal development and that it is still poorly understood. MeCP2 mutations alter its chromatin-binding dynamics and/or impair the ability of the protein to interact with some of its partners, resulting in Rett syndrome (RTT). Therefore, deciphering the molecular details involved in the MeCP2 neuronal chromatin arrangement is critical for our understanding of the proper and altered functionality of these cells.