CHD5
Domain
The PHD domains mediate specific binding to histone H3 unmethylated at 'Lys-4' and may preferentially recruit the protein to transcriptionally inactive genes.
The chromo domains mediate specific binding to histone H3 trimethylated at 'Lys-27' (H3K27me3) and may be required in neuron differentiation for proper gene regulation.
Function
Chromatin-remodeling protein that binds DNA through histones and regulates gene transcription. May specifically recognize and bind trimethylated 'Lys-27' (H3K27me3) and non-methylated 'Lys-4' of histone H3. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Plays a role in the development of the nervous system by activating the expression of genes promoting neuron terminal differentiation. In parallel, it may also positively regulate the trimethylation of histone H3 at 'Lys-27' thereby specifically repressing genes that promote the differentiation into non-neuronal cell lineages. Regulates the expression of genes involved in cell proliferation and differentiation. Downstream activated genes may include CDKN2A that positively regulates the p53/TP53 pathway, which in turn, prevents cell proliferation. In spermatogenesis, it probably regulates histone hyperacetylation and the replacement of histones by transition proteins in chromatin, a crucial step in the condensation of spermatid chromatin and the production of functional spermatozoa.
Involvement in disease
Defects in CHD5 may be a cause of the development of cancers from epithelial, neural and hematopoietic origin. CHD5 is one of the missing genes in the del(1p36), a deletion which is extremely common in this type of cancers. A decrease of its expression, results in increased susceptibility of cells to Ras-mediated transformation in vitro and in vivo (PubMed:17289567).
Parenti-Mignot neurodevelopmental syndrome
PMNDS
An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, speech delay, motor delay, behavioral problems, and epilepsy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Methylated at Gln-1390 by N6AMT1.
Sequence Similarities
Belongs to the SNF2/RAD54 helicase family.
Tissue Specificity
Preferentially expressed in total brain, fetal brain, and cerebellum. It is also moderately expressed in the adrenal gland and detected in testis.
Cellular localization
- Nucleus
- Chromosome
Alternative names
KIAA0444, CHD5, Chromodomain-helicase-DNA-binding protein 5, CHD-5, ATP-dependent helicase CHD5