Expression And Function Analysis Of Human Heart Development Related Novel Genes DTX2A And ZNF480

To a large extent, cellular differentiation is regulated by transcription factors. Several larger families of transcription factors have been identified, and in mammals, zinc finger proteins probably constitute the largest individual family of such nucleic acid - binding proteins. Here we have identified and characterized three novel zinc finger genes named DTX2A, ZNF480 and ZNF323 using degenerate primers from an early human embryo heart cDNA library. TheDTX2A mRNA is 2781 bp withll exons, which maps to chromosome 7q11.23 and spans approximately 44 kb. The predicted protein coded by DTX2A gene contains two WWE domains and a RING-finger, Northern analysis revealed that strong and week expression of the Deletx2A was found in adult human skeletal muscle,heart and placenta, pancreas, liver, respectively, and there is expression in embryonic heart, these results indicate that Deletx2A is involved in development of embryonic multiple organs. ZNF480 contain 4732bp. The cDNA sequence contains an open reading frame of 1551bp encoding a KRAB-BOX and 12 C2H2 fingers. Northern analysis predicted that strong expression was detected in adult heart and pancreas and its expression in skeletal, kidney, liver, placenta is week. But it is expressed only in the heart at six months embryo stage. Overexpression of ZNF480 in cells activates the transcriptional activities of AP-1 and SRE. The AP-1 and SRE are the important factors in the MAPK singal pathway, suggesting that the ZNF480protein may act as an active regulator in MAPK signaling pathway to mediate cellular functions.The ZNF323 mRNA is 3179 bp with 8 exons, which maps tochromosome 6p22. 1-22.3 and spans approximately 29. 45 kb. The predicted protein coded by ZNF323 gene contains six different krlipple 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 Z/VF323was 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. 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 is under way.