Characterization of a Novel Gene Encoding Zinc Finger Domains Identified from Expressed Sequence Tags (ESTs) of a Human Heart cDNA Database

Abstract

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 C2H2zinc 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 byin situhybridization revealed that this gene is in 19q13.1, a region containing genes involved in both cell cycle and developmental regulation.