Zider A, Mashhour B, Fergelot P, Grimber G, Vernet M, Hazan U, Couton D, Briand P, Cavard C
Laboratoire de Génétique et Pathologie Expérimentales, CJF INSERM 90-03, Institut Cochin de Génétique Moléculaire, Paris, France.
Nucleic Acids Res. 1993 Jan 11;21(1):79-86. doi: 10.1093/nar/21.1.79.
We have previously reported the epidermis-specific expression of the HIV-1 LTR in transgenic mice and its induction by UV-B rays. To dissect the underlying mechanism of the UV induction of the LTR in mice, we developed two approaches. We first demonstrated by gel mobility shift analysis, using mice epidermal extracts, that the NF-kappa B sites of the HIV-1 LTR were one of the targets of the UV induction. The Sp-1 sites and the potential AP-1 sites of the LTR were not involved in this phenomenon. The transient transfection assays of modified LTR in HeLa cells also demonstrated the involvement of the NF-kappa B sites in the UV induction and were consistent with previously published data. Secondly, to study the regulation acting on an integrated gene, we generated transgenic mice carrying the lacZ gene under the control of the partially deleted LTR. All the transgenic lines and unexpectedly those carrying the LTR deleted for the kappa B sites displayed a UV-inducible epidermal expression. This suggests that, in mice, the UV induction might be mediated through other sites than the kappa B sites and may also depend on changes of the chromatin state.
我们之前报道了HIV-1长末端重复序列（LTR）在转基因小鼠中的表皮特异性表达及其受UV-B射线诱导的情况。为了剖析小鼠中LTR受UV诱导的潜在机制，我们开发了两种方法。我们首先通过凝胶迁移率变动分析，利用小鼠表皮提取物证明HIV-1 LTR的NF-κB位点是UV诱导的靶点之一。LTR的Sp-1位点和潜在的AP-1位点不参与此现象。在HeLa细胞中对修饰后的LTR进行瞬时转染分析也证明了NF-κB位点参与UV诱导，并且与先前发表的数据一致。其次，为了研究对整合基因的调控作用，我们构建了在部分缺失的LTR控制下携带lacZ基因的转基因小鼠。所有转基因品系，出乎意料的是，那些携带缺失κB位点的LTR的品系也表现出UV诱导的表皮表达。这表明，在小鼠中，UV诱导可能通过κB位点以外的其他位点介导，也可能取决于染色质状态的变化。
