Piedrafita F J, Molander R B, Vansant G, Orlova E A, Pfahl M, Reynolds W F
Sidney Kimmel Cancer Center, San Diego, California 92121, USA.
J Biol Chem. 1996 Jun 14;271(24):14412-20. doi: 10.1074/jbc.271.24.14412.
An Alu element preceding the myeloperoxidase gene (MPO) contains four hexamer motifs related to the consensus recognition sequence for nuclear hormone receptors (AGGTCA), arranged as direct repeats with spacing of 2, 4, and 2 nucleotides (DR-2-4-2). Gel shift experiments and transient transfection assays demonstrate that these sequences include binding sites for retinoic acid and thyroid hormone receptors and function in vivo to activate transcription of a chloramphenicol acetyltransferase reporter gene. The first DR-2 elements of the series do not bind known receptors but do bind the SP1 transcription factor. Two alleles of the MPO gene exist that differ at one position within this element, resulting in one allele with and one without a strong SP1 binding site. The element with the SP1 site activates transcription by 25-fold in transient transfection assays, while the alternative allele confers severalfold less transcriptional activity. Most cases of acute myelocytic leukemia are homozygous for the allele with the SP1 binding site, suggesting this element plays an important role in regulating the MPO gene in myeloid leukemias. This MPO-Alu is a representative of an Alu subclass numbering approximately 400,000 copies, suggesting many genes may be regulated by such elements.
髓过氧化物酶基因（MPO）之前的一个Alu元件包含四个与核激素受体共有识别序列（AGGTCA）相关的六聚体基序，排列为直接重复序列，间隔为2、4和2个核苷酸（DR-2-4-2）。凝胶迁移实验和瞬时转染分析表明，这些序列包括视黄酸和甲状腺激素受体的结合位点，并在体内发挥作用以激活氯霉素乙酰转移酶报告基因的转录。该系列的第一个DR-2元件不结合已知受体，但结合SP1转录因子。MPO基因存在两个等位基因，在该元件内的一个位置不同，导致一个等位基因有一个强SP1结合位点，另一个则没有。在瞬时转染分析中，具有SP1位点的元件可将转录激活25倍，而另一个等位基因赋予的转录活性则低几倍。大多数急性髓细胞白血病病例对于具有SP1结合位点的等位基因是纯合的，这表明该元件在髓系白血病中调节MPO基因方面起重要作用。这个MPO-Alu是一个约有400,000个拷贝的Alu亚类的代表，这表明许多基因可能受此类元件调控。
