CHD5, a New Member of the Chromodomain Gene Family, is Preferentially Expressed in the Nervous System

Chromatin remodeling is one of the mechanisms by which gene expression is regulated developmentally. Chromatin structure is controlled at least in part by post-translational modification of histones, as well as by chromodomain proteins. We have identified a novel gene encoding a protein with chromatin remodeling, helicase and DNA-binding motifs. This gene, called CHD5, is the fifth member of the CHD gene family identified in humans. This gene is most homologous to CHD3 and CHD4, which encode proteins that are part of the nucleosome remodeling and histone deacetylation (NuRD) complex. CHD5 is preferentially expressed in total brain, fetal brain, and cerebellum. It is also moderately expressed in the adrenal gland, but expression is undetectable in almost all other tissues examined. CHD5 maps within a small region of deletion on 1p36.3 in human neuroblastomas, a common pediatric tumor. We examined a panel of neuroblastoma cell lines for CHD5 expression, which was consistently low or undetectable in all these lines. Expression was also examined in a panel of 137 primary neuroblastomas, and low expression was highly correlated with 1p deletion, MYCN amplification, advanced stage, and unfavorable histology. These findings suggest that this gene may play a role in the development of the nervous system, and it may also play a role in the pathogenesis of neural tumors.