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Loss or gain of copy number of the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2) leads to neurodevelopmental disorders (Rett and MeCP2 duplication syndrome), indicating that precisely regulated MeCP2 expression during development is critical for mental health. Consistent with this idea, MeCP2 null mutants exhibit synaptic regression in the dorsal lateral geniculate nucleus (dLGN), the visual relay center in the thalamus, a phenotype resembling that of animals reared in the dark during the visual sensitive period. It remains unclear how MeCP2 expression is regulated during circuit formation and maturation, especially in excitatory and inhibitory populations of neurons. We found that, concomitant with the initiation of the dark-rearing sensitive period, MeCP2 protein levels were elevated in glutamatergic but not GABAergic neurons of the dLGN. Moreover, MeCP2 expression in glutamatergic populations was selectively reduced by dark-rearing. Therefore, we propose that visual experience-dependent MeCP2 induction in glutamatergic populations is essential for synaptic maturation within the dLGN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976183 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198268 | PLOS |
Reprod Sci
September 2025
Department of Pathology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Background And Objective: As space exploration advances, the effects of the microgravity environment on testicular injury and spermatogenic function in astronauts have attracted widespread attention, but the underlying mechanisms remain unclear.
Methods: In this study, testicular morphometry and Johnsen score were used to evaluate the degree of testicular injury. Then the upstream transcription factors of MeCP2 were verified using the dual-luciferase reporter assay.
Orphanet J Rare Dis
September 2025
Unit of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Epicare Network for Rare Disease, Genoa, Italy.
Background: Rett Syndrome (RTT) is a rare, and severe neurodevelopmental disorder that primarily affects females and is primarily (> 96%) due to pathogenic loss-of-function genetic variants of methyl-CpG-binding protein 2 (MECP2). Despite the rarity of the syndrome, sporadic twin cases have been reported. The descriptions have often focused on the phenotype, emphasizing differences or similarities.
View Article and Find Full Text PDFiScience
September 2025
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
Recent discoveries showed that some chromatin-binding proteins also interact with RNA to regulate gene expression. Poly (ADP-ribose) polymerase 1 (PARP1) and methyl-CpG binding protein 2 (MeCP2) are two chromatin-associated, DNA-binding proteins that play central roles in gene expression, DNA damage response, and epigenetic regulation. Both proteins possess RNA-binding properties, but the mechanism by which PARP1 and MeCP2 recognize RNA-binding sites remains unclear.
View Article and Find Full Text PDFFront Drug Discov (Lausanne)
February 2025
Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, United States.
Introduction: Rett Syndrome is a genetic neurodevelopmental disorder caused by decreased levels of MeCP2. Due to mutations in the gene, insufficient MeCP2 protein levels lead to clinical phenotypes including the loss of normal movement, decreased communication, seizures, sleep disorders, and breathing problems. Currently there is no cure for Rett Syndrome and the only means to help patients is palliative care directed to their specific symptoms.
View Article and Find Full Text PDFCells
August 2025
Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Basic Medical Sciences Bldg. Room 627, Winnipeg, MB R3E 0J9, Canada.
Methyl CpG-binding protein 2 (MeCP2) is an epigenetic reader of DNA methylation with high abundance in the brain. While genetic mutations occur across different protein domains of MeCP2, the T158M mutation is amongst the most frequent MeCP2 mutations. MeCP2 is encoded by the / gene located on the X chromosome.
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