Cis-regulatory Function of the Pou5f1 Gene Promoter in the Mouse MHC Locus

The Pou5f1 gene encodes the Oct4 protein, one of the key transcription factors required for maintaining the pluripotent state of epiblast cells and the viability of germ cells. However, functional genetics provides convincing evidence that Pou5f1 has a broader range of functions in mouse ontogeny, including suppression of atherosclerotic processes. Related studies have primarily focused on the functions of the Oct4 protein, while the regulatory sequences within the Pou5f1 gene have not been considered. In this study, we have developed a genetic model which is based on mouse embryonic stem cells (ESCs) for assessing the roles of the Pou5f1 gene promoter in the transcriptional regulation of neighboring genes within the major histocompatibility complex (MHC) locus. We have demonstrated that deletion of this promoter affects the expression of selected genes within this locus neither in ESCs nor in the trophoblast derivatives of these cells. A notable exception is the Tcf19 gene, which is upregulated upon Pou5f1 promoter deletion and might be associated with the atherosclerosis pathology due to its pro-inflammatory activity. The developed genetic model will pave the way for future studies into the functional contribution of the cis-regulatory association of Pou5f1, Tcf19, and, possibly, other genes with the atherosclerotic phenotype previously reported for mice carrying the Pou5f1 promoter deletion in vascular endothelial and smooth muscle cells.