Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200 Brest, France.
Laboratoire de Génétique Moléculaire et d'Histocompatibilité, CHU Brest, F-29200 Brest, France.
Int J Mol Sci. 2023 Jun 26;24(13):10678. doi: 10.3390/ijms241310678.
More than 2000 variations are described within the () gene and related to large clinical issues from cystic fibrosis to mono-organ diseases. Although these -associated diseases have been well documented, a large phenotype spectrum is observed and correlations between phenotypes and genotypes are still not well established. To address this issue, we present several regulatory elements that can modulate gene expression in a tissue-specific manner. Among them, -regulatory elements act through chromatin loopings and take part in three-dimensional structured organization. With tissue-specific transcription factors, they form chromatin modules and can regulate gene expression. Alterations of specific regulations can impact and modulate disease expressions. Understanding all those mechanisms highlights the need to expand research outside the gene to enhance our knowledge.
在 () 基因内已经描述了 2000 多种变异，这些变异与从囊性纤维化到单器官疾病等大型临床问题有关。尽管这些与疾病相关的变异已经得到了很好的记录，但仍观察到很大的表型谱，并且表型和基因型之间的相关性尚未得到很好的建立。为了解决这个问题，我们提出了几个可以在组织特异性方式下调节 基因表达的调控元件。其中， - 调控元件通过染色质环化作用参与三维结构组织，并与组织特异性转录因子一起形成染色质模块，从而调节基因表达。特定调控的改变会影响和调节疾病的表现。了解所有这些机制突出表明需要扩展基因之外的研究，以增强我们的知识。
