The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders

Abstract

Chromodomain-helicase-DNA-binding protein 8 (CHD8) has been identified as one of the genes with the strongest association with autism. The CHD8 protein is a transcriptional regulator that is expressed in nearly all cell types and has been implicated in multiple cellular processes, including cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis. Considering the central role of CHD8 in the genetics of autism, a deeper understanding of the physiological functions of CHD8 is important to understand the development of the autism phenotype and potential therapeutic targets. Different CHD8 mutant mouse models were developed to determine autism-like phenotypes and to fully understand their mechanisms. Here, we review the current knowledge on CHD8, with an emphasis on mechanistic lessons gained from animal models that have been studied.

LINE-1 and Alu methylation signatures in autism spectrum disorder and their associations with the expression of autism-related genes

“…These results may be caused by disease-specific genetic variants of CHD8 that is a huge difference from the ASD without any genetic variants or with undefined ones. CHD8 is a chromatin remodeling/modifier factor that plays a role in the transcription process required for brain development 11 . LINE-1 and Alu elements have an activation and a repressive chromatin mark that is bound by several chromatin remodeling/modifier factors 39 , 42 , 47 , 58 .…”

“…People with 16p11.2del are usually characterized by developmental delay, intellectual disability, or ASD 9 . CHD8 is strongly associated with ASD and other neurodevelopmental disorders including schizophrenia and intellectual disability 10 , 11 .…”

Bioinformatics and next generation sequencing data analysis to identify key genes and pathways influencing in Parkinson’s disease

“…Signaling by NTRK1 (TRKA) [55], cardiac conduction [56], signaling by GPCR [57], immune system [58], cytokine signaling in immune system [59], interferon signaling [60] and toll-like receptor cascades [61] were responsible for development of PD. Recent studies have shown that EGR2 [62], WNT1 [63], ARC (activity regulated cytoskeleton associated protein) [64], CHRNA7 [65], SEZ6L2 [66], IL1RAPL2 [67], PER2 [68], PCDH19 [69], CNTNAP2 [70], SLC12A5 [71], CDK5 [72], ACTL6B [73], GABRD (gamma-aminobutyric acid type A receptor subunit delta) [74], CACNA1G [75], HTR2C [76], STX1A [77], ATP1A3 [78], RIMS3 [79], CNTNAP2 [80], CDH8 [81], SCAMP5 [82], SYNGR1 [83], ARHGEF9 [84], DLG3 [85], RBP4 [86], IL9 [87], S100A9 [88], HGF (hepatocyte growth factor) [89], C3 [90], FKBP5 [91], GABRE (gamma-aminobutyric acid type A receptor subunit epsilon) [92], NCKAP1L [93], PIK3CG [94], ITGB3 [95], ANXA1 [96], SYNE2 [97] and DBI (diazepam binding inhibitor, acyl-CoA binding protein) [98] were closely involved with the occurrence, development, and prognosis of autism spectrum disorder. EGR2 [99], ADCYAP1 [100], CHRNA7 [101], NRN1 [102], ETV5 [103], STXBP1 [104], CAMKK2 [105], VAMP2 [106], SYNGR1 [107], NOD2 [108], TLR2 [109], BRCA2 [110] and LEF1 [111] were previously reported to be critical for the development of bipolar disorder.…”

Progress in magnetic resonance imaging of autism model mice brain

“…Chromodomain-helicase-DNA-binding protein 8 (Chd8) is a transcriptional regulator (Weissberg & Elliott, 2021). It is involved in the regulation of the cell cycle, neuron development, myelination, synaptogenesis, and many other processes, and has been proven to be one of the genes most strongly related to autism (Hoffmann & Spengler, 2021).…”