Study of a novel gene, Hemogen/EDAG, in hematopoiesis and spermatogenesis.

摘要

Differential gene expression is the genetic basis of animal development. In the search for differentially expressed genes during early embryogenesis, a novel murine gene, Hemogen, has been cloned by cDNA subtraction, and the human homologue EDAG has also been identified. The Hemogen /EDAG gene encodes a novel nuclear protein. Developmental studies show that this gene transcribes into at least two distinct mRNA isoforms. One isoform marks the ontogeny of hematopoiesis in which the transcripts exhibit specific and sequential location in the active hematopoietic sites, such as blood islands, fetal liver and bone marrow. This gene is expressed in hematopoietic stem/progenitor cells and then restricted in erythroid and megakaryocytic lineages. Another distinct mRNA isoform is specifically expressed in round spermatids of the testis. These results suggest a role of Hemogen /EDAG gene in hematopoiesis and spermatogenesis.;The transcription of Hemogen/EDAG gene into hematopoietic and testicular mRNA isoforms is regulated through the use of alternative promoters and polyadenylation sites. Although the coding regions are identical, the 5' and 3' UTRs of these two isoforms are distinct. To further define the regulatory elements, we have analyzed the promoter of the hematopoietic isoform to demonstrate that two GATA-binding sites are critical for the promoter activity in K562 cells, suggesting GATA-mediated regulation is important for Hemogen gene expression. This Hemogen promoter fragment exhibits hematopoietic specificity when transfected into various cell lines.;We have assigned Hemogen gene to mouse chromosome 4 A5-B2 and EDAG gene to a syntenic region, human chromosome 9q22. Interestingly, these chromosome locations are associated with leukemia breakpoints. A knockout construct has been made to disrupt the Hemogen gene, and three targeted ES clones have been obtained. Further research is in progress to generate knockout mice to delineate the function of Hemogen in vivo. The study of Hemogen/EDAG gene provides a window to investigate the developmental processes, such as hematopoiesis and spermatogenesis, and the related diseases.