Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Department of Oncology, Odense University Hospital, Odense, Denmark.
PLoS One. 2018 Oct 10;13(10):e0205461. doi: 10.1371/journal.pone.0205461. eCollection 2018.
Drosophila DNA replication-related element binding factor (DREF) is a transcription regulatory factor that binds the promoters of many genes involved in replication and cell proliferation and is required for normal cell cycle progression. Human DREF/zinc finger BED domain-containing protein 1 (ZBED1), an orthologue of Drosophila DREF, also has DNA binding activity, but its cellular functions remain largely uncharacterized. Herein, we show that ZBED1 is a chromatin-associated nuclear protein with a wide expression profile in human tissues from all three primary germ layers. For instance, ZBED1 was expressed in mesodermal-derived epithelial cells of the reproductive system and urinary tract, in endodermal-derived epithelial cells throughout the gastrointestinal tract, and in epidermal epithelium from the ectoderm. ZBED1 was also expressed in connective tissue and smooth muscle cells of multiple organs. To investigate whether ZBED1 is implicated in cell proliferation, similar to Drosophila DREF, we compared the tissue distribution of ZBED1 to that of the proliferation marker Ki-67. ZBED1 and Ki-67 were co-expressed in many epithelial tissues, but ZBED1 expression extended widely beyond that of Ki-67-positive cells. In other tissues, ZBED1 expression was more restricted than Ki-67 expression. These results suggest that ZBED1 is not a cell proliferation-associated factor such as Drosophila DREF, and our study adds to the cumulative understanding of the functions of ZBED1 in human cells and tissues.
果蝇 DNA 复制相关元件结合因子（DREF）是一种转录调控因子，它结合许多与复制和细胞增殖相关的基因的启动子，是正常细胞周期进程所必需的。果蝇 DREF 的同源物人类 DREF/锌指 BED 结构域包含蛋白 1（ZBED1）也具有 DNA 结合活性，但它的细胞功能在很大程度上仍未被阐明。本文中，我们表明 ZBED1 是一种与染色质相关的核蛋白，在来自三个初级胚层的人类组织中具有广泛的表达谱。例如，ZBED1 在生殖系统和泌尿道的中胚层衍生的上皮细胞、整个胃肠道的内胚层衍生的上皮细胞以及外胚层的表皮上皮细胞中表达。ZBED1 还在多个器官的结缔组织和平滑肌细胞中表达。为了研究 ZBED1 是否像果蝇 DREF 一样参与细胞增殖，我们将 ZBED1 的组织分布与增殖标志物 Ki-67 进行了比较。ZBED1 和 Ki-67 在许多上皮组织中共同表达，但 ZBED1 的表达范围远远超出了 Ki-67 阳性细胞。在其他组织中，ZBED1 的表达比 Ki-67 的表达更为局限。这些结果表明，ZBED1 不是像果蝇 DREF 那样的与细胞增殖相关的因子，我们的研究增加了对 ZBED1 在人类细胞和组织中的功能的综合认识。
