Al-Obaide Mohammed A, Islam Saimul, Al-Obaidi Ibtisam, Vasylyeva Tetyana L
Department of Pediatrics, Texas Tech University Health Sciences Center, Amarillo, TX, United States.
Front Genet. 2023 Dec 13;14:1229088. doi: 10.3389/fgene.2023.1229088. eCollection 2023.
Fabry disease (FD) is a rare genetic condition caused by mutations in the gene, located on the X chromosome in the readthrough genomic region. This gene produces an enzyme called alpha-galactosidase A (α-Gal A). When the enzyme does not function properly due to the mutations, it causes harmful substances called globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to build up in the body's lysosomes. This accumulation can damage the kidneys, heart, eyes, and nervous system. Recent studies have shown that the readthrough loci, which include and genes, as well as the regulatory sequence known as the bidirectional promoter, may also play a role in FD. However, the involvement of enhancer RNAs (eRNAs) in FD is still poorly understood despite their known role in various diseases. To investigate this further, we studied an enhancer called GH0XJ101390 and showed its genomic setting in the readthrough region; the eRNA is rich in Homotypic Clusters of TFBSs (HCTs) type and hosts a CpG Island (CGI). To test the functional correlation further with , , and , we used siRNAs to knock down GH0XJ101390 in human kidney embryonic cells 293T. The results showed a significant decrease in and expression and a non-significant decrease in expression. These findings could have important implications for understanding the regulatory mechanisms of GH0XJ101390 and its potential role in FD. A better understanding of these mechanisms may improve diagnostic and therapeutic methods for FD, which could ultimately benefit patients with this rare condition.
法布里病（FD）是一种罕见的遗传性疾病，由位于X染色体通读基因组区域的基因突变引起。该基因产生一种名为α-半乳糖苷酶A（α-Gal A）的酶。当由于突变导致该酶功能不正常时，会使名为Globotriaosylceramide（Gb3）和Globotriaosylsphingosine（lyso-Gb3）的有害物质在人体溶酶体中蓄积。这种蓄积会损害肾脏、心脏、眼睛和神经系统。最近的研究表明，包括[具体基因1]和[具体基因2]基因以及被称为[双向启动子名称]的双向启动子在内的通读位点，可能也在FD中起作用。然而，尽管增强子RNA（eRNA）在各种疾病中的作用已为人所知，但它们在FD中的参与情况仍知之甚少。为了进一步研究这一点，我们研究了一种名为GH0XJ101390的增强子，并展示了其在通读区域的基因组背景；该eRNA富含TFBSs同型簇（HCTs）类型，并拥有一个CpG岛（CGI）。为了进一步测试其与[具体基因1]、[具体基因2]和[具体基因3]的功能相关性，我们使用小干扰RNA（siRNAs）在人肾胚胎细胞293T中敲低GH0XJ101390。结果显示[具体基因1]和[具体基因2]的表达显著下降，而[具体基因3]的表达下降不显著。这些发现可能对理解GH0XJ101390的调控机制及其在FD中的潜在作用具有重要意义。更好地理解这些机制可能会改善FD的诊断和治疗方法，最终使患有这种罕见疾病的患者受益。
