EGR1 Regulates SHANK3 Transcription at Different Stages of Brain Development.
Neuroscience
; 540: 27-37, 2024 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-38218401
ABSTRACT
The expression levels of SHANK3 are associated with autism spectrum disorder (ASD). The dynamic changes in SHANK3 expression during different stages of brain development may impact the progression of ASD. However, no studies or detailed analyses exploring the upstream mechanisms that regulate SHANK3 expression have been reported. In this study, we employed immunofluorescence to examine the expression of SHANK3 in brain organoids at various stages. Our results revealed elevated levels of SHANK3 expression in brain-like organoids at Day 60. Additionally, we utilized bioinformatics software to predict and analyze the SHANK3 gene's transcription start site. Through the dual luciferase reporter gene technique, we identified core transcription elements within the SHANK3 promoter. Site-directed mutations were used to identify specific transcription sites of SHANK3. To determine the physical binding of potential transcription factors to the SHANK3 promoter, we employed electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Our findings demonstrated that the transcription factor EGR1 regulates SHANK3 expression by binding to the transcription site of the SHANK3 promoter. Although this study did not investigate the pathological phenotypes of human brain organoids or animal model brains with EGR1 deficiency, which could potentially substantiate the findings observed for SHANK3 mutants, our findings provide valuable insights into the relationship between the transcription factor, EGR1, and SHANK3. This study contributes to the molecular understanding of ASD and offers potential foundations for precise targeted therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastorno del Espectro Autista
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neuroscience
Año:
2024
Tipo del documento:
Article
País de afiliación:
China