Dai K S, Liew C C
Institute of Medical Science and Department of Laboratory Medicine and Pathobiology, The Centre for Cardiovascular Research, The Toronto Hospital, University of Toronto, Ontario, Canada.
J Mol Cell Cardiol. 1998 Nov;30(11):2365-75. doi: 10.1006/jmcc.1998.0797.
Seven types of zinc finger protein (ZFP) genes based on the combinations of cysteine and histidine residues were found in a human heart cDNA database. Here we report the isolation of 360 cDNA clones encoding putative ZFPs. Of these, 154 (42.8%) represent C2H2-type ZFPs, 101 (28.1%) represent C2C2-type, five (1.4%) represent C2HC-type, 71 (19.7%) represent C2HC4C(HD)-type, three (0.8%) represent C3H-type, eight (2.2%) represent C3HC4-type and 18 (0.5%) represent combination type (genes containing more than one type of zinc finger). Among these 360 ZFPs, a novel ZFP cDNA named HFHZ (human fetal heart ZFP) with sequence homology to a Kruppel-associated box (KRAB) was identified. Sequencing the full-length of this cDNA clone identified an open reading frame of 711 bp that encodes a 237 amino acid protein with a predicted molecular weight of 27.7 kDa. Sequence analysis indicated that HFHZ contained a truncated KRAB box at the N-terminus and two C2H2 zinc fingers at the C-terminus. The transcript of HFHZ is highly expressed in fetal heart and moderately expressed in fetal brain but not expressed in fetal liver as revealed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis suggesting that HFHZ is not expressed ubiquitously. The 3.3-fold higher expression in the fetal heart than in the adult heart suggests that HFHZ mRNA is downregulated in the process of development. In addition, the relatively high expression (1.9-fold) of HFHZ observed in the hypertrophic as compared to the normal adult heart suggests that this fetal gene is reactivated in response to hypertrophic stimuli. Chromosomal localization by in situ hybridization revealed that this gene is in 19q13.1, a region containing genes involved in both cell cycle and developmental regulation.
在人类心脏cDNA数据库中发现了基于半胱氨酸和组氨酸残基组合的七种锌指蛋白（ZFP）基因。在此，我们报告了360个编码假定ZFP的cDNA克隆的分离情况。其中，154个（42.8%）代表C2H2型ZFP，101个（28.1%）代表C2C2型，5个（1.4%）代表C2HC型，71个（19.7%）代表C2HC4C(HD)型，3个（0.8%）代表C3H型，8个（2.2%）代表C3HC4型，18个（0.5%）代表组合型（包含一种以上锌指类型的基因）。在这360个ZFP中，鉴定出一个与Kruppel相关盒（KRAB）具有序列同源性的新型ZFP cDNA，命名为HFHZ（人类胎儿心脏ZFP）。对该cDNA克隆的全长进行测序，确定了一个711 bp的开放阅读框，其编码一个237个氨基酸的蛋白质，预测分子量为27.7 kDa。序列分析表明，HFHZ在N端包含一个截短的KRAB盒，在C端包含两个C2H2锌指。逆转录-聚合酶链反应（RT-PCR）分析显示，HFHZ的转录本在胎儿心脏中高度表达，在胎儿脑中中度表达，但在胎儿肝脏中不表达，这表明HFHZ并非普遍表达。胎儿心脏中的表达比成年心脏高3.3倍，这表明HFHZ mRNA在发育过程中被下调。此外，与正常成年心脏相比，在肥厚性成年心脏中观察到HFHZ相对较高的表达（1.9倍），这表明该胎儿基因在肥厚性刺激下被重新激活。原位杂交的染色体定位显示，该基因位于19q13.1，该区域包含参与细胞周期和发育调控的基因。
