Forced expression of Genesis, a winged helix transcriptional repressor isolated from embryonic stem cells, blocks granulocytic differentiation of 32D myeloid cells

Abstract

We recently isolated and characterized a novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis. Genesis was found to be a transcriptional repressor expressed almost exclusively in embryonic stem cells or embryonal carcinoma cells. This expression rapidly declined when these cells were stimulated to differentiate. This expression pattern suggested that Genesis may play a role in cellular differentiation. To explore that possibility in a heterologous system of differentiation, Genesis was stably transduced into the IL-3-dependent myeloid cell line 32D using a retroviral expression vector. 32D cells over-expressing Genesis failed to mature normally when stimulated with G-CSF but continued to proliferate and maintained a primitive phenotype. This finding implicates Genesis in the regulation of development, and also implies that there may be common transcription pathways for many developing tissues.