REV7参与各种生物过程，包括DNA修复与突变、细胞周期调控、基因转录以及癌变。REV7在成人睾丸生殖细胞以及多种恶性肿瘤中高度表达。REV7表达水平与多种人类癌症的预后相关，然而REV7转录调控机制尚未阐明。本研究对REV7基因的启动子区域进行了表征。利用人类生殖细胞瘤细胞系NEC8进行荧光素酶报告基因检测，检查REV7上游基因组区域的转录活性，并鉴定了两个转录激活区域。我们利用定向点突变确定了一个小的基因组区域对于转录激活很重要；这个区域共享了几个转录因子结合位点，包括cAMP响应元素调节剂(CREM)，cAMP响应元素结合蛋白(CREB)和B淋巴细胞诱导分化蛋白-1(BLIMP-1)。在NEC8细胞或人类胚胎肾细胞系HEK293T中，外源CREM和CREB表达对转录活性没有效果。相反，外源BLIMP-1表达增加了HEK293T细胞中的荧光素酶报告活性，但在NEC8细胞中却意外地降低了活性。染色质免疫沉淀分析表明，BLIMP-1结合到REV7启动子附近的基因组区域。此外，BLIMP-1过表达促进了HEK293T细胞内源性REV7的表达。这些发现表明，BLIMP-1可能是哺乳动物细胞中REV7的潜在转录调节因子。版权所有©2023 Elsevier Inc.

REV7 is involved in various biological processes including DNA repair and mutagenesis, cell cycle regulation, gene transcription, and carcinogenesis. REV7 is highly expressed in adult testicular germ cells as well as several malignant tumors. REV7 expression levels are associated with prognosis in several human cancers, however, the mechanism of REV7 transcriptional regulation has not been elucidated. In this study, we characterized the promoter region of the REV7 gene. A luciferase reporter assay using the human germ cell tumor cell line NEC8 was utilized to examine the upstream genomic region of REV7 for transcriptional activity, and two transcriptional activation regions were identified. We determined a small genomic region important for transcriptional activation using site-directed mutagenesis; this region is shared by several putative binding motifs for transcription factors, including the cAMP-responsive element modulator (CREM), cAMP-response element binding protein (CREB), and B-lymphocyte-induced maturation protein-1 (BLIMP-1). Exogenous CREM and CREB expression had no effect on the transcriptional activity in NEC8 cells or the human embryonic kidney cell line HEK293T. In contrast, exogenous BLIMP-1 expression increased luciferase reporter activity in HEK293T cells but unexpectedly decreased activity in NEC8 cells. Chromatin immunoprecipitation analysis demonstrated that BLIMP-1 binds to the genomic region near the binding motif in the REV7 promoter. Additionally, BLIMP-1 overexpression promoted endogenous REV7 expression in HEK293T cells. These findings suggest that BLIMP-1 may be a putative transcriptional regulator of REV7 in mammalian cells.Copyright © 2023 Elsevier Inc. All rights reserved.