Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway
Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway
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DOI：
10.1128/mcb.25.15.6559-6569.2005
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Chrivia, JC
中科院分区：
文献类型：
--
作者：
Eissenberg, JC;Wong, M;Chrivia, JC
通过与组蛋白乙酰化酶CBP的相互作用，在酵母双杂交蛋白筛选中鉴定了推定的ATP酶染色质重塑机器SRCAP。SRCAP与环AMP和类固醇依赖性启动子的转录共激活有关，但尚未确定SRCAP调控的天然染色体靶点。DOM是果蝇中唯一的SRCAP同源物。本研究的目的是测试SRCAP是否是DOM的功能同源物，并确定SRCAP在体内的潜在活性和靶点。我们表明，人类SRCAP互补隐性多米诺突变表型。这种拯救依赖于完整的ATP酶同源结构域。SRCAP与DOM广泛共定位于果蝇多线染色体上，并被招募到活跃转录的位点，如类固醇调节的位点，但不被招募到活化的热休克位点。我们发现，SRCAP招聘果蝇CBP异位染色体位点，提供了第一个证据表明，SRCAP和CBP直接或间接地在染色体上相互作用。我们表明，DOM是一个Notch途径激活剂在果蝇和野生型SRCAP-但不是ATP酶结构域突变体-可以取代DOM的Notch依赖的翅膀发育。我们发现，SRCAP增强了HeLa细胞中Notch依赖的基因激活。总之，这些数据暗示SRCAP和DOM在发育基因激活。
The putative ATPase chromatin-remodeling machine SRCAP was identified in a yeast two-hybrid protein screen by interaction with the histone acetylase CBP. SRCAP is implicated in the transcriptional coactivation of cyclic AMP- and steroid-dependent promoters, but no natural chromosomal targets for SRCAP regulation have been identified. DOM is the unique SRCAP homolog in Drosophila melanogaster. The goal of this study was to test whether SRCAP is a functional homolog of DOM and to identify potential activities and targets of SRCAP in vivo. We show that human SRCAP complements recessive domino mutant phenotypes. This rescue depends on an intact ATPase homology domain. SRCAP colocalizes extensively with DOM on Drosophila polytene chromosomes and is recruited to sites of active transcription, such as steroid-regulated loci, but not to activated heat shock loci. We show that SRCAP recruits Drosophila CBP to ectopic chromosomal sites, providing the first evidence to suggest that SRCAP and CBP interact directly or indirectly on chromosomes. We show that DOM is a Notch pathway activator in Drosophila and that wild-type SRCAP-but not an ATPase domain mutant-can substitute for DOM in Notch-dependent wing development. We show that SRCAP potentiates Notch-dependent gene activation in HeLa cells. Taken together, these data implicate SRCAP and DOM in developmental gene activation.