Thompson Patricia M, Gotoh Takahiro, Kok Marleen, White Peter S, Brodeur Garrett M
Division of Oncology, the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Oncogene. 2003 Feb 20;22(7):1002-11. doi: 10.1038/sj.onc.1206211.
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.
染色质重塑是基因表达在发育过程中受到调控的机制之一。染色质结构至少部分受组蛋白的翻译后修饰以及色域蛋白的控制。我们鉴定出了一个新基因,它编码一种具有染色质重塑、解旋酶和DNA结合基序的蛋白质。这个名为CHD5的基因是在人类中鉴定出的CHD基因家族的第五个成员。该基因与CHD3和CHD4最为同源,CHD3和CHD4编码的蛋白质是核小体重塑和组蛋白去乙酰化(NuRD)复合物的一部分。CHD5在全脑、胎儿脑和小脑中优先表达。它在肾上腺中也有适度表达,但在几乎所有其他检测的组织中均未检测到表达。CHD5定位于人类神经母细胞瘤(一种常见的儿科肿瘤)1p36.3的一个小缺失区域内。我们检测了一组神经母细胞瘤细胞系中的CHD5表达,在所有这些细胞系中其表达始终很低或检测不到。我们还检测了137例原发性神经母细胞瘤中的表达,低表达与1p缺失、MYCN扩增、晚期和不良组织学高度相关。这些发现表明该基因可能在神经系统发育中起作用,也可能在神经肿瘤的发病机制中起作用。