Vrijens Karen, Van Camp Guy, Van Laer Lut
Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Antwerp, Belgium.
Gene. 2009 Mar 1;432(1-2):82-90. doi: 10.1016/j.gene.2008.11.017. Epub 2008 Nov 27.
Mutations in DFNA5 cause a non-syndromic autosomal dominant type of hearing loss. Although not much is known regarding the physiological function of DFNA5, it is not only related to hearing loss. A clear link with cancer exists. For example, methylation of the 5' flanking region of DFNA5 was detected in breast, colorectal and gastric cancer. So far, this 5' flanking region has not been studied in detail. Here, we describe the identification of the cochlear transcription initiation site (TIS), the identification of the core promoter region between -120 and +70 relative to the TIS and the identification of an enhancer (between -121 and -356 bp) and a silencer element (between -356 and -670 bp). Results were similar in HEK293 cells and in the organ of Corti cell line OC-k3. Transfection with a reversely-oriented construct resulted in high transcriptional activity. We subsequently confirmed this antisense activity and identified a novel antisense transcript partly overlapping Dfna5.
DFNA5基因的突变会导致一种非综合征性常染色体显性听力损失。尽管目前对DFNA5的生理功能了解不多，但它不仅与听力损失有关，还与癌症存在明确的联系。例如，在乳腺癌、结直肠癌和胃癌中都检测到了DFNA5基因5'侧翼区域的甲基化。到目前为止，这个5'侧翼区域尚未得到详细研究。在此，我们描述了耳蜗转录起始位点（TIS）的鉴定、相对于TIS在-120至+70之间核心启动子区域的鉴定以及一个增强子（在-121至-356 bp之间）和一个沉默子元件（在-356至-670 bp之间）的鉴定。在HEK293细胞和柯蒂氏器细胞系OC-k3中的结果相似。用反向构建体转染导致高转录活性。我们随后证实了这种反义活性，并鉴定出一种部分与Dfna5重叠的新型反义转录本。
