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

Depression perception; MYT1L mice; brain signal variability DOI

Jill Adams

The Transmitter, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Citations

0
Molecular changes after MECP2 loss may drive Rett syndrome traits DOI
Chloe Williams

The Transmitter, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
MECP2 mRNA Profile in Brain Tissues from a Rett Syndrome Patient and Three Human Controls: Mutated Allele Preferential Transcription and In Situ RNA Mapping DOI Creative Commons

Martina Mietto,

Silvia Montanari, Maria Sofia Falzarano

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 687 - 687

Published: May 8, 2025

Rett syndrome (RTT) is a rare X-linked dominant neurodevelopmental disorder caused by pathogenic variants in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes (MeCP2) that acts as repressor of gene expression, crucial neurons. Dysfunction MeCP2 due to its explains clinical features RTT. Here, we performed histological and RNA analyses on post-mortem brain sample from an RTT patient carrying p.Arg106Trp missense mutation. This part cohort 56 genetically clinically characterized patients, for whom provide overview mutation landscape. In specimen, RT-PCR analysis detected preferential transcription mutated mRNA. X-inactivation studies revealed skewed X-chromosome inactivation ratio (95:5), supporting transcriptional findings. We also mapped MECP2 transcript control human regions (temporal cortex cerebellum) using RNAscope assay, confirming high expression. study reports representation and, first time, situ localization brain, offering insights into how specific mutations may differentially impact neuronal functions. suggest these findings are developing RNA-based therapies syndrome.

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
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

Citations

1