Developmental roles of the Mi-2/NURD-Associated protein p66 in Drosophila
Developmental roles of the Mi-2/NURD-Associated protein p66 in Drosophila
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DOI：
10.1534/genetics.104.034595
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发表时间：
2005-04-01
期刊：
影响因子：
3.3
通讯作者：
Nusse, R
中科院分区：
文献类型：
--
作者：
Kon, C;Cadigan, KM;Nusse, R
NURD 和 Sin3 组蛋白脱乙酰酶复合物通过染色质的整体脱乙酰化参与转录抑制。两种复合物都含有许多不同的成分，可以控制组蛋白脱乙酰酶复合物的调节方式以及与其他转录因子的相互作用。在果蝇眼中无翅信号修饰因子的遗传筛选中，我们分离了果蝇 p66 同源物中的突变，p66 是一种先前作为非洲爪蟾 NURD/Mi-2 复合物一部分纯化的蛋白质。 p66 编码发育所需的高度保守的核锌指蛋白，我们建议 p66 蛋白充当 NURD 复合物的调节成分。 p66 纯合突变体动物在变态过程中表现出缺陷，这可能是由蜕皮激素调节的表达失调引起的。尽管p66的杂合性增强了眼睛中的无翼表型，但翼和眼盘中功能丧失的克隆没有任何可检测到的表型，这可能是由于Sin3复合体的冗余所致。另一方面，p66 的过度表达可以抑制无翅依赖性表型。此外，p66 表达可以在细胞培养测定中抑制多个报告基因，包括 Wnt 响应性 TCF 报告基因构建体，表明 NURD 复合物参与了 Writ 靶基因的抑制。通过免疫共沉淀，p66 与已知的 NURD 复合体成员 dMi-2 结合。
The NURD and Sin3 histone deacetylase complexes are involved in transcriptional repression through global deacetylation of chromatin. Both complexes contain many different components that may control how histone deacetylase complexes are regulated and interact with other transcription factors. In a genetic screen for modifiers of wingless signaling in the Drosophila eye, we isolated mutations in the Drosophila homolog of p66, a protein previously purified as part of the Xenopus NURD/Mi-2 complex. p66 encodes a highly conserved nuclear zinc-finger protein that is required for development and we propose that the p66 protein acts as a regulatory component of the NURD complex. Animals homozygous mutant for p66 display defects during metamorphosis possibly caused by misregulation of ecdysone-regulated expression. Although heterozygosity for p66 enhances a wingless phenotype in the eye, loss-of-function clones in the wing and the eye discs do not have any detectable phenotype, possibly due to redundancy with the Sin3 complex. Overexpression of p66, on the other hand, can repress wingless-dependent phenotypes. Furthermore, p66 expression can repress multiple reporters in a cell culture assay, including a Wnt-responsive TCF reporter construct, implicating the NURD complex in repression of Writ target genes. By co-immunoprecipitation, p66 associates with dMi-2, a known NURD complex member.