Menin Deficiency Induces Autism-Like Behaviors by Regulating Foxg1 Transcription and Participates in Foxg1-Related Encephalopathy.
Adv Sci (Weinh)
; 11(24): e2307953, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38582517
ABSTRACT
FOXG1 syndrome is a developmental encephalopathy caused by FOXG1 (Forkhead box G1) mutations, resulting in high phenotypic variability. However, the upstream transcriptional regulation of Foxg1 expression remains unclear. This report demonstrates that both deficiency and overexpression of Men1 (protein menin, a pathogenic gene of MEN1 syndrome known as multiple endocrine neoplasia type 1) lead to autism-like behaviors, such as social defects, increased repetitive behaviors, and cognitive impairments. Multifaceted transcriptome analyses revealed that Foxg1 signaling is predominantly altered in Men1 deficiency mice, through its regulation of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (Atrx) factor. Atrx recruits menin to bind to the transcriptional start region of Foxg1 and mediates the regulation of Foxg1 expression by H3K4me3 (Trimethylation of histone H3 lysine 4) modification. The deficits observed in menin deficient mice are rescued by the over-expression of Foxg1, leading to normalized spine growth and restoration of hippocampal synaptic plasticity. These findings suggest that menin may have a putative role in the maintenance of Foxg1 expression, highlighting menin signaling as a potential therapeutic target for Foxg1-related encephalopathy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Modelos Animais de Doenças
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Fatores de Transcrição Forkhead
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article