Alternative promoters and polyadenylation regulate tissue-specific expression of Hemogen isoforms during...

Hemogen is a nuclear protein encoded by HEMGN (also known as hemogen in mouse, EDAG in human and RP59 in rat). It is considered to be a hematopoiesis-specific gene that is expressed during the ontogeny of hematopoiesis. Herein, we characterize two distinct splicing variants of HEMGN mRNA with restricted expression to hematopoietic cells and to round spermatids in the testis, respectively. Expression of the testis-specific HEMGN mRNA (HEMGN-t) is developmentally regulated and is concurrent with the first wave of meiosis in prepuberal mice. Sequence analysis reveals that HEMGN-t and the hematopoietic HEMGN mRNA (HEMGN-h) share a common coding sequence with distinct 5' and 3' untranslated regions and that these two isoforms are transcribed from the same gene locus, HEMGN, through the use of alternative promoters and polyadenylation sites. Thus, HEMGN expression exemplifies a developmental regulatory mechanism by which the diversification of gene expression is achieved through using distinct regulatory sequences in different cell types. Moreover, the existence of a testis-specific isoform of HEMGN suggests a role in spermatogenesis. Finally, fluorescence in situ hybridization demonstrates that HEMGN is localized to chromosome 4 A5-B2 in mouse and to chromosome 9q22 in human, which is a region known to harbor a cluster of leukemia breakpoints.