CHD8 : chromodomain helicase DNA binding protein 8
Description
The CHD8 (chromodomain helicase DNA binding protein 8) is a protein-coding gene located on chromosome 14.
The CHD8 gene provides instructions for making a protein that regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed. Chromatin remodeling is one way gene expression is regulated during development. The CHD8 protein is thought to affect the expression of many other genes that are involved in brain development before birth. In particular, the CHD8 protein and the genes it regulates likely help control the development of neural progenitor cells, which give rise to nerve cells (neurons), and the growth and division (proliferation) and maturation (differentiation) of neurons. In this way, the CHD8 protein helps to control the number of neurons in the brain and prevent overgrowth.
CHD8 is a DNA helicase that acts as a chromatin remodeling factor and regulates gene transcription. It acts as a transcription repressor by altering chromatin structure and recruiting histone H1 to target genes. CHD8 suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. It functions as a negative regulator of the Wnt signaling pathway by controlling beta-catenin (CTNNB1) activity. CHD8 negatively regulates CTNNB1-targeted gene expression by specifically binding to the promoter regions of several CTNNB1 responsive genes. It is involved in both enhancer blocking and epigenetic remodeling at chromatin boundaries through its interaction with CTCF. CHD8 acts as a suppressor of STAT3 activity by suppressing LIF-induced STAT3 transcriptional activity. It also acts as a transcription activator through its interaction with ZNF143, participating in efficient U6 RNA polymerase III transcription. CHD8 regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle, and DNA repair. It enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL.
CHD8 is also known as AUTS18, HELSNF1, IDDAM.
Associated Diseases
- Intellectual developmental disorder with autism and macrocephaly
- 14q11.2 microduplication syndrome
- Autism spectrum disorder
