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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
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i-Motif,而不是G-quadruplex,稳定性可以调节胰岛素的表达.

Dilek Guneri1,2, Christopher J Morris1, Yiliang Ding3

  • 1School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.

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概括

人类胰岛素基因的转录激活需要G-四重复和i-动机结构形成. 促进子活性与i-动机稳定性相关,这表明基因调节中的动态相互作用.

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科学领域:

  • 遗传学 遗传学是一种遗传学.
  • 分子生物学分子生物学
  • 生物物理学的生物物理.

背景情况:

  • 胰岛素链接多态区域 (ILPR) 是人类胰岛素基因促进体中的可变并列重复.
  • ILPR序列可以形成G-四复合体 (G4) 和i-动机 (IM),DNA结构与基因调节有关.
  • 在调节胰岛素基因表达方面,G4和IM的确切作用,特别是当它们同时发生时,尚未完全理解.

研究的目的:

  • 研究ILPR序列多样性,DNA结构形成 (G4和IM) 和胰岛素基因调节之间的关系.
  • 为了确定G4和IM结构在响应葡萄糖时影响转录活性的条件.
  • 阐明G4和IM结构在调节胰岛素基因促进活性中的特定作用.

主要方法:

  • 使用生物物理技术对九个基于ILPR的DNA序列进行了表征.
  • 对DNA结构稳定性和形成的评估.
  • 路西法酶记者测试在不同的葡萄糖条件下测量促进体活性.

主要成果:

  • 胰岛素基因促进体的转录激活仅在G-四重复和i-动机结构都能形成时才被观察到.
  • 胰岛素基因促进活性与i-motif稳定性呈正相关性,但与G-四重复性稳定性并非如此.
  • 不同的G4和IM结构组合不诱导转录,突出显示了这两种结构的必要性.

结论:

  • 提出了一个模型,其中G-四重复可能启动转录,而i-动机调节胰岛素基因表达.
  • 形成和稳定G-四复合体和i-动机对于对葡萄糖反应的胰岛素基因调节至关重要.
  • 这些DNA结构代表了一个动态的,相互依赖的系统,有可能成为基因表达调制的治疗点.