CHD5

This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]

Full Name

Chromodomain Helicase DNA Binding Protein 5

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. 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. Tumor suppressor, it 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.

Biological Process

Cerebral cortex neuron differentiation Source: UniProtKB
Histone H3-K27 trimethylation Source: UniProtKB
Histone H4 acetylation Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Positive regulation of signal transduction by p53 class mediator Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Spermatogenesis, exchange of chromosomal proteins Source: UniProtKB

Cellular Location

Nucleus. Associates with heterochromatin.

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).

PTM

Methylated at Gln-1390 by N6AMT1.