Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase.
Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase.
复制标题
I 类组蛋白脱乙酰酶对组织特异性和细胞外基质相关基因的调节。
DOI：
10.1016/j.molcel.2005.04.006
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Shi,Yang
中科院分区：
文献类型：
--
作者：
Whetstine,JohnathanR;Ceron,Julian;Ladd,Brendon;Dufourcq,Pascale;Reinke,Valerie;Shi,Yang
I 类组蛋白脱乙酰酶 (HDAC) 通过组蛋白脱乙酰化来抑制转录，并已被证明在小鼠、非洲爪蟾、斑马鱼和线虫中发挥着至关重要的作用。秀丽隐杆线虫的发展。为了确定多细胞生物体中 I 类 HDAC 调节的分子网络，我们使用 C 进行了全局基因表达谱研究。线虫胚胎，并确定组织特异性和细胞外基质 (ECM) 相关基因作为 HDA-1 的主要靶标。 HDA-1 orC 的异位表达。 eleganscystatin 是从微阵列中鉴定出的 HDA-1 靶标，可显着扰乱哺乳动物细胞的侵袭。同样，RNAi 耗竭或人 HDAC-1 过度表达也会影响细胞迁移。这些发现表明 HDA-1/HDAC-1 可能在调节细胞外微环境中发挥关键的、进化上保守的作用。由于人类 HDAC 是癌症治疗的靶点，因此这些发现对癌症治疗具有重要意义。
Class I histone deacetylases (HDACs) repress transcription by deacetylating histones and have been shown to play crucial roles in mouse,Xenopus, zebrafish, andC. elegansdevelopment. To identify the molecular networks regulated by a class I HDAC in a multicellular organism, we carried out a global gene expression profiling study usingC. elegansembryos, and identified tissue-specific and extracellular matrix (ECM)-related genes as major HDA-1 targets. Ectopic expression of HDA-1 orC. eleganscystatin, an HDA-1 target identified from the microarray, significantly perturbed mammalian cell invasion. Similarly, RNAi depletion or overexpression of human HDAC-1 also affected cell migration. These findings suggest that HDA-1/HDAC-1 may play a critical, evolutionarily conserved role in regulating the extracellular microenvironment. Because human HDACs are targets for cancer therapy, these findings have significant implications in cancer treatment.