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

TL;DR

This study explores how the Pou5f1 gene promoter regulates nearby genes in mouse embryonic stem cells and its potential role in atherosclerosis.

Contribution

The paper introduces a genetic model to study the cis-regulatory role of the Pou5f1 promoter in the MHC locus.

Findings

Deletion of the Pou5f1 promoter does not affect most neighboring genes in ESCs or trophoblast derivatives.

The Tcf19 gene is upregulated after Pou5f1 promoter deletion, potentially linking it to atherosclerosis.

The model can help investigate how Pou5f1 and Tcf19 contribute to atherosclerosis in vascular cells.

Abstract

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.

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