Epigenetic Regulation and Neurodevelopmental Disorders: From MeCP2 to the TCF20/PHF14 Complex DOI Open Access

G Dominguez,

Yongji Wu, Jian Zhou

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(12), P. 1653 - 1653

Published: Dec. 23, 2024

Background: Neurodevelopmental disorders (NDDs) affect approximately 15% of children and adolescents worldwide. This group is often polygenic with varying risk factors, many associated genes converging on shared molecular pathways, including chromatin regulation transcriptional control. Understanding how NDD-associated regulators protein complexes orchestrate these regulatory pathways crucial for elucidating NDD pathogenesis developing targeted therapeutic strategies. Recently, the TCF20/PHF14 complex was identified in mammalian brain, expanding list remodelers implicated NDDs. complex—which includes MeCP2, RAI1, TCF20, PHF14, HMG20A—plays a vital role epigenetic regulation. Methods: We review summarize current research clinical reports pertaining to different components MeCP2-interacting complex. examine NDDs complex, explore neuronal functions its components, discuss emerging strategies targeting this mitigate symptoms, broader applicability other Results: Mutations encoding have been linked various NDDs, underscoring critical contribution brain development pathogenesis. Conclusions: The could serve as model system provide insight into interplay between

Language: Английский

Cell type–specific 3D-genome organization and transcription regulation in the brain DOI Creative Commons

Shiwei Liu,

Cosmos Yuqi Wang, Pu Zheng

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(9)

Published: Feb. 26, 2025

3D organization of the genome plays a critical role in regulating gene expression. How 3D-genome differs among different cell types and relates to type–dependent transcriptional regulation remains unclear. Here, we used genome-scale DNA RNA imaging investigate transcriptionally distinct mouse cerebral cortex. We uncovered wide spectrum differences nuclear architecture types, ranging from size nucleus higher-order chromosome structures radial positioning chromatin loci within nucleus. These variations exhibit strong correlations with both total activity type–specific marker genes. Moreover, found that methylated binding protein MeCP2 promotes active-inactive segregation regulates transcription position–dependent manner is highly correlated its function modulating compartmentalization.

Language: Английский

Citations

2
Interaction of methyl-CpG-binding protein 2 (MeCP2) with distinct enhancers in the mouse cortex DOI
Gyan Prakash Mishra,

Eric Sun,

Tan Yew Chin

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Language: Английский

Citations

4
Effects of MeCP2 on chronic seizures and cognitive function in mice with temporal lobe epilepsy DOI
Yu Chen,

Shu-Nan Yang,

Guan-Ling Fu

et al.

Epilepsy Research, Journal Year: 2025, Volume and Issue: 210, P. 107512 - 107512

Published: Jan. 20, 2025

Language: Английский

Citations

0
Versatile functions of methyl-CpG-binding domain 2 (MBD2) in cellular characteristics and differentiation DOI

Rabia Tuana Lekesiz,

Kerim Koca,

Gizem Kugu

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 15, 2025

Language: Английский

Citations

0
MeCP2 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types DOI

J. Russell Moore,

Mati Nemera, Rinaldo D. D’Souza

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Language: Английский

Citations

0
Exploring the complexity of MECP2 function in Rett syndrome DOI
Yi Liu, Troy W. Whitfield, George W. Bell

et al.

Nature reviews. Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: May 13, 2025

Language: Английский

Citations

0
Interpreting the rich dialogue between astrocytes and neurons: An overview in Rett syndrome DOI Creative Commons

Francesca Maddalena Postogna,

Ottavia Maria Roggero, Fabio Biella

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 227, P. 111386 - 111386

Published: May 15, 2025

Language: Английский

Citations

0
MeCP2 Interacts with the Super Elongation Complex to Regulate Transcription DOI Creative Commons
Jun Young Sonn, Wonho Kim, Marta Iwanaszko

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Loss-of-function mutations in methyl-CpG binding protein 2 (

Language: Английский

Citations

3
Identification of early Alzheimer’s disease subclass and signature genes based on PANoptosis genes DOI Creative Commons
Wen-Xu Wang,

Jincheng Lu,

Ning Pan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 22, 2024

Introduction Alzheimer’s disease (AD) is one of the most prevalent forms dementia globally and remains an incurable condition that often leads to death. PANoptosis represents emerging paradigm in programmed cell death, integrating three critical processes: pyroptosis, apoptosis, necroptosis. Studies have shown necroptosis, pyroptosis play important roles AD development. Therefore, targeting genes might lead novel therapeutic targets clinically relevant approaches. This study aims identify different molecular subtypes potential drugs for treating based on PANoptosis. Methods Differentially expressed associated with were identified via Gene Expression Omnibus (GEO) dataset GSE48350, GSE5281, GSE122063. Least Absolute Shrinkage Selection Operator (LASSO) regression was employed construct a risk model linked these genes. Consensus clustering analysis conducted define We further performed gene set variation (GSVA), functional enrichment analysis, immune infiltration investigate differences between subtypes. Additionally, protein-protein interaction (PPI) network established hub genes, DGIdb database consulted compounds Single-cell RNA sequencing utilized assess expression at cellular level across Results A total 24 differentially (APANRGs) AD, leading classification two distinct subgroups. The results indicate subgroups exhibit varying progression states, early subtype primarily dysfunctional synaptic signaling. Furthermore, we from (DEGs) clusters predicted 38 candidate treatment revealed key are predominantly neuronal cells, while differential metabolic found endothelial cells astrocytes. Conclusion In summary, subtypes, including abnormality as well immune-metabolic subtype. ten SLC17A7, SNAP25, GAD1, SLC17A6, SLC32A1, PVALB, SYP, GRIN2A, SLC12A5, SYN2, marker These findings may provide valuable insights diagnosis contribute development innovative strategies.

Language: Английский

Citations

3
Human MeCP2 binds to promoters and inhibits transcription in an unmethylated S. cerevisiae genome DOI Open Access
LeAnn J. Howe, Joshua A.R. Brown, Juan Ausió

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

MeCP2 is a DNA-binding transcriptional regulator that present at near-histone levels in mammalian cortical neurons. Originally identified as DNA methylation reader, has been proposed to repress transcription by recruiting corepressors methylated DNA. While some genome-wide occupancy studies support preference for DNA, others suggest binding more influenced sequence and accessibility than status. Moreover, multiple also role gene activation. To clarify function we expressed Saccharomyces cerevisiae , which lacks known corepressors. We find toxic yeast globally inhibits transcription, indicating can have significant functional impacts without or A subset of mutations cause the neurodevelopmental disorder Rett syndrome, particularly those map domain, alleviate toxicity yeast. Consistent with importance yeast, show binds genome, increased GC-rich, nucleosome-depleted sequences. These findings useful tool analyzing reveal properties are not strictly dependent on

Language: Английский

Citations

1