Meignin Carine, Dastugue Bernard, Vaury Chantal
Unité INSERM 384, BP38, 63001 Clermont-Ferrand, France.
Nucleic Acids Res. 2004 Jul 19;32(13):3799-806. doi: 10.1093/nar/gkh708. Print 2004.
ZAM is an long terminal repeat (LTR) retrotransposon from Drosophila melanogaster that bears striking resemblance to the vertebrate retroviruses, in their structure and replication cycle. This element transposes via an RNA intermediate and its reverse transcription, and ultimately inserts copies within the germ line. In this paper, we show that intercellular communication established between the germ line cells and the somatic follicle cells is used to initiate the replication cycle of ZAM. ZAM has been shown to be transcribed in the follicle cells located at the posterior pole of the oocyte. Here, we determine the cis-regulatory elements necessary for its somatic expression, and show that they respond to the EGF-receptor signaling pathway and its activation by the ligand Gurken emitted by the germ line. We further show that the ETS-transcription factor Pointed2 acting downstream of this pathway acts as a trans-regulatory factor and targets a specific cis-regulatory binding site located within the ZAM LTR. Our data give an insight into the molecular mechanism for how intercellular communications between germ cells and somatic cells may be used by endogenous retroviruses to control their replication, and thereby specify their intrinsic and highly restricted expression in the reproductive apparatus.
ZAM是一种来自黑腹果蝇的长末端重复序列(LTR)逆转座子,在结构和复制周期上与脊椎动物逆转录病毒有显著相似性。该元件通过RNA中间体及其逆转录进行转座,并最终在生殖系中插入拷贝。在本文中,我们表明生殖系细胞和体细胞卵泡细胞之间建立的细胞间通讯被用于启动ZAM的复制周期。已证明ZAM在位于卵母细胞后极的卵泡细胞中进行转录。在这里,我们确定了其体细胞表达所需的顺式调控元件,并表明它们对表皮生长因子受体信号通路以及生殖系发出的配体Gurken对其的激活作出反应。我们进一步表明,在该信号通路下游起作用的ETS转录因子Pointed2作为反式调控因子,靶向位于ZAM LTR内的一个特定顺式调控结合位点。我们的数据深入揭示了生殖细胞和体细胞之间的细胞间通讯如何被内源性逆转录病毒用于控制其复制,从而在生殖器官中确定其固有且高度受限的表达的分子机制。