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首页> 外文期刊>Molecular and Cellular Biology >Chromatin-Mediated Restriction of Nuclear Factor 1/CTF Binding in a Repressed and Hormone-Activated Promoter In Vivo
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Chromatin-Mediated Restriction of Nuclear Factor 1/CTF Binding in a Repressed and Hormone-Activated Promoter In Vivo

机译：染色质介导的抑制和激素激活的启动子体内的核因子1 / CTF绑定的限制。

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摘要

Mouse mammary tumor virus (MMTV) promoter-driven transcription is induced by glucocorticoid hormone via binding of the glucocorticoid receptor (GR). The MMTV promoter also harbors a binding site for nuclear factor 1 (NF1). NF1 and GR were expressed in Xenopus oocytes; this revealed GR-NF1 cooperativity both in terms of DNA binding and chromatin remodeling but not transcription. A fraction of NF1 sites were occupied in a hormone-dependent fashion, but a significant and NF1 concentration-dependent fraction were constitutively bound. Activation of the MMTV promoter resulted in an ～50-fold increase in the NF1 accessibility for its DNA site. The hormone-dependent component of NF1 binding was dissociated by addition of a GR antagonist; however, the antagonist RU486, which supports partial GR-DNA binding, also maintained partial NF1 binding. Hence GR-NF1 cooperativity is independent of agonist-driven chromatin remodeling. NF1 induced the formation of a micrococcal-nuclease-resistant protein-DNA complex containing the DNA segment from ?185 to ?55, the MMTV enhanceosome. Coexpression of NF1 and Oct1 resulted in a significant stimulation of hormone-induced MMTV transcription and also in increased basal transcription. We propose that hormone-independent NF1 binding may be involved in maintaining transcriptional competence and establishment of tissue-specific gene networks.
机译：糖皮质激素通过糖皮质激素受体（GR）的结合来诱导小鼠乳腺肿瘤病毒（MMTV）启动子驱动的转录。 MMTV启动子还带有核因子1（NF1）的结合位点。 NF1和GR在非洲爪蟾卵母细胞中表达。这揭示了GR-NF1在DNA结合和染色质重塑方面的协同性，但在转录方面没有。一部分NF1位点以激素依赖性方式被占据，但是一个显着的和NF1浓度依赖性部分被组成性结合。 MMTV启动子的激活导致其DNA位点的NF1可及性增加了约50倍。通过添加GR拮抗剂可解除NF1结合的激素依赖性成分。然而，支持部分GR-DNA结合的拮抗剂RU486也维持了部分NF1结合。因此，GR-NF1的协同作用独立于激动剂驱动的染色质重塑。 NF1诱导了抗微球菌核酸酶的蛋白质-DNA复合物的形成，该复合物含有MMTV增强体，从185到55的DNA片段。 NF1和Oct1的共表达导致激素诱导的MMTV转录的显着刺激，也增加了基础转录。我们建议激素非依赖性的NF1绑定可能参与维持转录能力和组织特异性基因网络的建立。

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