Studies On Human Zinc-finger Transcription Factors And Heart Embryonic Development

The krupple type zinc finger motif found in many transcription factors is thought to be important for nucleic acid binding and/or dimerization. Here we have identified and characterized two novel zinc finger genes named ZNF323 and ZNF360 using degenerate primers from an early human embryo heart cDNA library. The ZNF323 mRNA is 3179 bp with 8 exons, which maps to chromosome 6p22.1-22.3 and spans approximately 29.45 kb. The predicted protein coded by ZNF323 gene contains six different krtlpple type zinc fingers and a SCAN box. The expression levels were different during different development stages of human embryo between 18 weeks and 25 weeks. Northern blot analysis shows that a 3. 2 kb transcript specific for ZNF323 was expressed at high levels in the lung, liver, and kidney, while weakly expressed in intestine, brain, muscle, cholecyst, heart, and pancreas. In adult tissues, ZNF323 is expressed at high level in liver and kidney, weakly in lung, pancreas, brain, plancenta, muscle, and heart. The ZNF360 mRNNA is 4031 bp, which spans 17. 3 kb and is organized into eight exons. The preduced protein coded by ZNF360 gene contains 977 amino acids, including a KRAB motif, a SCAN motif, two SANT motifs and ten krtlpple type zinc fingers. The ZNF360 gene is wildly expressed in the various tissues of human embryos, especially in kidney, heart and lung. The complete human ZNF359 cDNA sequence is 3270 bp and contains a 1932 bp open reading frame (ORF) that encodes a 643 amino acid protein with an N-terminal KRAB domain and 16 C-terminus zinc finger C2H2 motifs. The ZFP28 cDNA sequence is 4104 bp and contains a 2076 bp ORF that encodes and 868 amino acids protein with an N-terminal signal peptide, two KRAB domain, and 14 C-termianal C2H2 zinc finger motifs. Northern blot analyses showed a strong expression of ZNF359 and ZFP28 in various tissues of adult human. A further analysis using human embryonictissues (18-23 weeks) showed a development-specific expression pattern in heart, skeletal muscle, liver, lung, kidney, and brain. Taken together, these results indicate that these genes are members of zinc finger transcription factor family and may be involved in the development of multiple embryonic organs. We collected drug abortive early embryos, the rate of malformation was 17. 86% and the rate of early embryonic lethality was 32. 54%. The early embryo were made into a series of continuous section slides by tissue cutting. The sections were stained by Hematoxylin and Eosin (H&E) staining and then the development of internal organs such as heart in early embryos was observed by microscope. We found that there is certain relationship between external and internal malformation. Further study on this point was under way.