The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes

Transl Psychiatry. 2015 May 19;5(5):e568. doi: 10.1038/tp.2015.62.


Chromodomain helicase DNA-binding protein 8 (CHD8) was identified as a leading autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and subsequent targeted-sequencing studies. De novo loss-of-function mutations were identified in 12 individuals with ASD and zero controls, accounting for a highly significant association. Small interfering RNA-mediated knockdown of CHD8 in human neural progenitor cells followed by RNA sequencing revealed that CHD8 insufficiency results in altered expression of 1715 genes, including both protein-coding and noncoding RNAs. Among the 10 most changed transcripts, 4 (40%) were noncoding RNAs. The transcriptional changes among protein-coding genes involved a highly interconnected network of genes that are enriched in neuronal development and in previously identified ASD candidate genes. These results suggest that CHD8 insufficiency may be a central hub in neuronal development and ASD risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autism Spectrum Disorder / genetics
  • Autistic Disorder / genetics*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Humans
  • Neural Stem Cells / metabolism*
  • RNA, Messenger / genetics*
  • RNA, Small Interfering
  • RNA, Untranslated / genetics*
  • Transcription Factors / genetics*


  • CHD8 protein, human
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA, Untranslated
  • Transcription Factors