Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, IN 46202-5122, United States.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, IN 46202-5122, United States; Department of Medical and Molecular Genetics, Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, IN 46202-5122, United States.
Gene. 2014 Sep 1;547(2):239-44. doi: 10.1016/j.gene.2014.06.047. Epub 2014 Jun 24.
The class IV alcohol dehydrogenase gene ADH7 encodes an enzyme that is involved in ethanol and retinol metabolism. ADH7 is expressed mainly in the upper gastrointestinal tract and not in the liver, the major site of expression of the other closely related ADHs. We identified an intergenic sequence (iA1C), located between ADH7 and ADH1C, that has enhancer-blocking activity in liver-derived HepG2 cells that do not express their endogenous ADH7. This enhancer blocking function was cell- and position-dependent, with no activity seen in CP-A esophageal cells that express ADH7 endogenously. iA1C function was not specific to the ADH enhancers; it had a similar cell-specific effect on the SV40 enhancer. The CCCTC-binding factor (CTCF), an insulator binding protein, bound iA1C in HepG2 cells but not in CP-A cells. Our results suggest that in liver-derived cells, iA1C blocks the effects of ADH enhancers and thereby contributes to the cell specificity of ADH7 expression.
IV 类醇脱氢酶基因 ADH7 编码的酶参与乙醇和视黄醇代谢。ADH7 主要在上消化道表达，而不在肝脏表达，肝脏是其他密切相关的 ADHs 的主要表达部位。我们鉴定了一个基因间序列（iA1C），位于 ADH7 和 ADH1C 之间，它在不表达内源性 ADH7 的肝源性 HepG2 细胞中具有增强子阻断活性。这种增强子阻断功能具有细胞和位置依赖性，在表达 ADH7 的 CP-A 食管细胞中没有活性。iA1C 的功能不是 ADH 增强子所特有的；它对 SV40 增强子也有类似的细胞特异性效应。结合蛋白绝缘子结合蛋白 CCCTC 结合因子（CTCF）在 HepG2 细胞中结合 iA1C，但在 CP-A 细胞中不结合。我们的结果表明，在肝源性细胞中，iA1C 阻断了 ADH 增强子的作用，从而有助于 ADH7 表达的细胞特异性。
