Identification of a novel transcription factor, ELYS, expressed predominantly in mouse foetal haematopoietic tissues

Background: The precise mechanism governing the generation of haematopoietic stem cells still remains to be understood, partly because the molecules required for early haematopoiesis have not fully been identified. Results: We have identified a novel gene expressed in embryonic haematopoietic tissues, designated ELYS (for embryonic large molecule derived from yolk sac), which has no significant homology with any other known molecules. Based on the cDNA sequence, mouse ELYS protein is composed of 2243 amino acid residues and contains an AT-hook DNA-binding domain, eight nuclear localization signals (NLSs) at the C-terminal region, three nuclear export signals (NESs) and two WD repeats at the N-terminal region. ELYS has a potential to shuttle between the cytoplasm and nucleus. When in the nucleus, ELYS is present in the nuclear matrix. Fusions of the yeast GAL4 DNA-binding domain and various ELYS mutants reveal the presence of transcriptional activation and inhibitory domains. The ELYS gene is predominantly expressed in embryonic haematopoietic tissues, i.e. foetal liver, spleen, and thymus, whereas the expression is down-regulated in the adult. In the aorta-gonad-mesonephros (AGM) region of an 11.5 dpc mouse embryo, ELYS is expressed in the endothelium lining the dorsal aorta. In the adult bone marrow, ELYS is notably expressed in the Lin^-/c-kit⁺/Sca-1⁺ population. Conclusions: We have reported the isolation and characterization of a novel molecule, ELYS. ELYS seems to be a nuclear transcription factor associated with both early and mature haematopoietic events.