77 / 2024-10-19 16:07:17

A novel epigenetic mechanism of ADNP resides in postnatal neurons

ADNP,postnatal,Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a genetically heterogeneous neurodevelopmental disorder with core symptoms of social communication deficits and repetitive stereotyped behaviors. Activity-dependent neuroprotective protein (ADNP), a modulator of chromatin remodeling highly expressed in the brain, is one of the most frequently mutated genes in ASD. The evidence on the epigenetic mechanism of ADNP in the central nervous system (CNS) has hitherto focused on the embryonic stage, however, we found that ADNP exhibits disparate localization patterns in the postnatal neurons, indicating a stage specificity exists. To investigate the postnatal function of ADNP, we constructed conditional knock-out mice and found that loss of ADNP leads to developmental delays, dysrhythmias, and anxiety-depression-like phenotypes, which are typical symptoms in the patients. By RNA-sequencing, we observed an enrichment of upregulated genes in the transcription regulation and nuclear acid binding pathway. In the future, we will explore the changes of histone modification and chromatin accessibility by combining ChIP-seq and ATAC-seq, and further decipher the potential regulation of ADNP on the three-dimensional structure of the genome through Hi-C. Our work aims at complement the epigenetic mechanism of ADNP in the pathogenesis of ASD and provide a new theoretical basis for the diagnosis and treatment.