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Engrailed与Nejire共同作用以控制卵巢干细胞微环境中的表达。

Engrailed acts with Nejire to control expression in the ovarian stem cell niche.

作者信息

Luo Lichao, Siah Chia Keng, Cai Yu

机构信息

Temasek Life Sciences Laboratory, National University of Singapore, 117604 Singapore.

Department of Biological Sciences, National University of Singapore, 117543 Singapore.

出版信息

Development. 2017 Sep 15;144(18):3224-3231. doi: 10.1242/dev.145474.

Abstract

Homeostasis of adult tissues is maintained by a small number of stem cells, which are sustained by their niches. In the female germline stem cell (GSC) niche, Decapentaplegic (Dpp) is the primary factor that promotes GSC self-renewal. However, the mechanism regulating expression in the niche is largely unknown. Here, we identify a 2.0 kb fragment located in a 5' -regulatory region of the locus containing enhancer activity that drives its expression in the niche. This region is distinct from a previously characterized 3' -regulatory enhancer responsible for expression in imaginal discs. Our data demonstrate that Engrailed, a homeodomain-containing transcription factor that serves as a cap cell marker, binds to this region and regulates expression in cap cells. Further data suggest that En forms a complex with Nejire (Nej), the ortholog of histone acetyltransferase CBP/p300, and directs Nej to this -regulatory region where Nej functions as the co-activator for expression. Therefore, our study defines the molecular pathway controlling expression in the ovarian stem cell niche.

摘要

成体组织的稳态由少量由其微环境维持的干细胞来保持。在雌性生殖系干细胞(GSC)微环境中,骨形态发生蛋白(Dpp)是促进GSC自我更新的主要因子。然而,调节其在微环境中表达的机制很大程度上尚不清楚。在这里,我们鉴定出一个位于该基因座5′调控区域的2.0 kb片段,其具有增强子活性,可驱动其在微环境中的表达。该区域不同于先前鉴定的负责在成虫盘表达的3′调控增强子。我们的数据表明,作为帽细胞标记物的含同源结构域转录因子Engrailed与该区域结合并调节帽细胞中的表达。进一步的数据表明,Engrailed与组蛋白乙酰转移酶CBP/p300的直系同源物Nejire(Nej)形成复合物,并将Nej引导至该调控区域,在那里Nej作为表达的共激活因子发挥作用。因此,我们的研究确定了控制卵巢干细胞微环境中表达的分子途径。

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