The mitochondrial S-adenosylmethionine carrier (SAMC), encoded by the SLC25A26 gene, catalyzes the uptake of S-adenosylmethionine (SAM) from the cytosol into mitochondria in exchange for S-adenosylhomocysteine (SAH), produced inside the mitochondria. In the last years we have been functionally characterizing the promoter of SLC25A26 gene. In this study we show that a silencer activity is present in the region from −756 bp to −504 bp, which specifically binds a protein present in Caski cells nuclear extracts. By in silico analysis, EMSA, ChIP, overexpressing and silencing experiments this protein was identified as FOXD3 which acts as a repressor of SLC25A26 expression. Interestingly, the repressor activity of FOXD3 is completely abolished by treating Caski cells with folate via a mechanism that involves methylation of FOXD3 gene promoter. This finding could have important impact in cancer cells where SLC25A26 is downregulated. Finally, the DPE and INR putative sites were also identified.

由SLC25A26基因编码的线粒体S-腺苷甲硫氨酸载体（SAMC）催化S-腺苷甲硫氨酸（SAM）从细胞质进入线粒体，以交换在线粒体内产生的S-腺苷同型半胱氨酸（SAH）。在最近几年中，我们一直在功能上表征SLC25A26基因的启动子。在这项研究中，我们表明，在-756 bp至-504 bp的区域中存在沉默子活性，该沉默子活性与Caski细胞核提取物中存在的蛋白特异性结合。由in silico经分析，EMSA，ChIP，过表达和沉默实验，该蛋白被鉴定为FOXD3，可作为SLC25A26表达的阻遏物。有趣的是，通过一种涉及FOXD3基因启动子甲基化的机制，用叶酸处理Caski细胞可以完全消除FOXD3的阻遏物活性。这一发现可能对SLC25A26被下调的癌细胞产生重要影响。最后，还确定了DPE和INR推定位点。