Characterization of the CHD family of proteins
Characterization of the CHD family of proteins
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DOI：
10.1073/pnas.94.21.11472
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发表时间：
1997-10-14
影响因子：
11.1
通讯作者：
Collins, FS
中科院分区：
文献类型：
--
作者：
Woodage, T;Basrai, MA;Collins, FS
鼠基因CHD 1（MmCHD 1）先前在寻找结合DNA启动子元件的蛋白质时分离。Chrome（染色质组织修饰剂）结构域和SNF 2相关的解旋酶/ATP酶结构域的存在导致推测该基因调节染色质结构或基因转录。本研究描述了三个新的人类基因MmCHD 1相关的克隆和表征。序列数据库的检查产生了几个更多的相关基因，其中大多数是不知道是类似于MmCHD 1，产生了12个高度保守的CHD基因，从生物体的酵母和哺乳动物。序列变异的主要区域是在蛋白质的C-末端部分，MmCHD 1中具有DNA结合活性的区域。SsCHD 1，唯一的酿酒酵母CHD基因的靶向缺失，进行与缺失菌株比野生型对6-氮尿嘧啶的细胞毒性作用不敏感。这一发现表明，由于6-azauracil诱导的核苷酸贫乏耗尽，RNA聚合酶II暂停位点的转录停滞增强在缺失菌株中减少，并且ScCHD 1抑制转录。这一观察结果，沿着其他蛋白质与Chrome或SNF 2相关的解旋酶/ATP酶结构域的已知作用，表明CHD基因的基因表达改变可能通过染色质结构的修饰发生，改变了转录装置对其染色体DNA模板的访问。
The murine gene CHD1 (MmCHD1) was previously isolated in a search for proteins that bound a DNA promoter element. The presence of chrome (chromatin organization modifier) domains and an SNF2-related helicase/ATPase domain led to speculation that this gene regulated chromatin structure or gene transcription. This study describes the cloning and characterization of three novel human genes related to MmCHD1. Examination of sequence databases produced several more related genes, most of which were not known to be similar to MmCHD1, yielding a total of 12 highly conserved CHD genes from organisms as diverse as yeast and mammals. The major region of sequence variation is in the C-terminal part of the protein, a region with DNA-binding activity in MmCHD1. Targeted deletion of SsCHD1, the sole Saccharomyces cerevesiae CHD gene, was performed with deletion strains being less sensitive than wild type to the cytotoxic effect of 6-azauracil. This finding suggested that enhanced transcriptional arrest at RNA polymerase II pause sites due to 6-azauracil-induced nucleotide poor depletion was reduced in the deletion strain and that ScCHD1 inhibited transcription. This observation, along with the known roles of other proteins with chrome or SNF2-related helicase/ATPase domains, suggests that alteration of gene expression by CHD genes might occur by modifications of chromatin structure, with altered access of the transcriptional apparatus to its chromosomal DNA template.