Oct transcription factors in development and stem cells: insights and mechanisms

Abstract

The POU domain family of transcription factors regulates developmental processes ranging from specification of the early embryo to terminal differentiation. About half of these factors display substantial affinity for an 8 bp DNA site termed the octamer motif, and are hence known as Oct proteins. Oct4 (Pou5f1) is a well-known Oct factor, but there are other Oct proteins with varied and essential roles in development. This Primer outlines our current understanding of Oct proteins and the regulatory mechanisms that govern their role in developmental processes and concludes with the assertion that more investigation into their developmental functions is needed.

Keywords: Oct proteins; POU domain; Stem cells.

Fig. 1.

Modes of Oct protein transcriptional regulation. The binding of Oct protein (green) to a target gene depends on the presence of a sequence-specific binding site (gray rectangle) and involves the POU_H and POU_S domains (light green) within the Oct protein, which are connected via a linker sequence (see Box 1). (A) Gene activation. The Oct protein activates the expression of its target genes (green arrows) either directly by promoting the assembly of a transcription complex at the promoter or indirectly by acting through the nucleosomes (pink). In the latter case, the Oct protein interacts with co-factors (blue) to deposit positively acting chromatin modifications (small green circles) or to remove repressive marks (small red circles). ATP-dependent chromatin remodeling may also be employed (not shown). Active gene expression (black arrow on the DNA) is typically associated with promoter DNA that is free of cytosine methylation (white circles). (B) Poising of transcriptionally silent genes. Targets genes of Oct1 and Oct4, and perhaps other Oct proteins, can be transcriptionally silent (red X) but epigenetically poised to rapidly initiate expression upon reception of the correct developmental cues. Present evidence indicates that the Oct protein mechanism in gene poising is positive, removing repressive modifications. The effect of chromatin on gene expression can be differentiated from that in A because a mixture of positively and negatively acting modifications is present (simultaneous green and red arrows). These genes typically lack DNA methylation (white circles). (C) Gene repression. In this case, the Oct protein recruits co-repressor activities that remove activating marks or deposit repressive marks on the chromatin to repress gene transcription (red arrow). These genes are typified by a high degree of promoter DNA methylation (black circles).