Fourel Geneviève, Magdinier Frédérique, Gilson Eric
CNRS/ENSL/INRA UMR 5161, 46 Allée d'Italie, Ecole Normale Supérieure de Lyon, 69364 Lyon cedex 07, France.
Bioessays. 2004 May;26(5):523-32. doi: 10.1002/bies.20028.
The early discovery of cis-regulatory elements able to promote transcription of genes over large distances led to the postulate that elements, termed insulators, should also exist that would limit the action of enhancers, LCRs and silencers to defined domains. Such insulators were indeed found during the past fifteen years in a wide range of organisms, from yeast to humans. Recent advances point to an important role of transcription factors in insulator activity and demonstrate that the operational observation of an insulator effect relies on a delicate balance between the "efficiency" of the insulator and that of the element to be counteracted. In addition, genuine insulator elements now appear less common than initially envisaged, and they are only found at loci displaying a high density of coding or regulatory information. Where this is not the case, chromatin domains of opposing properties are thought to confront each other at "fuzzy" boundaries. In this article, we propose models for both fixed and fuzzy boundaries that incorporate probabilistic and dynamic parameters.
顺式调控元件能够远距离促进基因转录这一早期发现,引发了这样一种假设,即应该也存在一种元件(称为绝缘子),它会将增强子、LCR(基因座控制区)和沉默子的作用限制在特定结构域内。在过去十五年间,确实在从酵母到人类等广泛的生物体中发现了此类绝缘子。最近的进展表明转录因子在绝缘子活性中发挥着重要作用,并证明绝缘子效应的实际观察依赖于绝缘子与要被抵消的元件之间“效率”的微妙平衡。此外,真正的绝缘子元件现在看来比最初设想的要少见,并且仅在显示出高密度编码或调控信息的基因座中发现。在不存在这种情况的地方,具有相反特性的染色质结构域被认为在“模糊”边界处相互对峙。在本文中,我们提出了包含概率和动态参数的固定边界和模糊边界模型。