The Gene for the Embryonic Stem Cell Coactivator UTF1 Carries a Regulatory Element Which Selectively Interacts with a Complex Composed of Oct-3/4 and Sox-2

Abstract

UTF1 is a transcriptional coactivator which has recently been isolated and found to be expressed mainly in pluripotent embryonic stem (ES) cells (A. Okuda, A. Fukushima, M. Nishimoto, et al., EMBO J. 17:2019-2032, 1998). To gain insight into the regulatory network of gene expression in ES cells, we have characterized the regulatory elements governing UTF1 gene expression. The results indicate that the UTF1 gene is one of the target genes of an embryonic octamer binding transcription factor, Oct-3/4. UTF1 expression is, like the FGF-4 gene, regulated by the synergistic action of Oct-3/4 and another embryonic factor, Sox-2, implying that the requirement for Sox-2 by Oct-3/4 is not limited to the FGF-4 enhancer but is rather a general mechanism of activation for Oct-3/4. Our biochemical analyses, however, also reveal one distinct difference between these two regulatory elements: unlike the FGF-4 enhancer, the UTF1 regulatory element can, by its one-base difference from the canonical octamer-binding sequence, selectively recruit the complex comprising Oct-3/4 and Sox-2 and preclude the binding of the transcriptionally inactive complex containing Oct-1 or Oct-6. Furthermore, our analyses reveal that these properties are dictated by the unique ability of the Oct-3/4 POU-homeodomain that recognizes a variant of the Octamer motif in the UTF1 regulatory element.

Stem cell pluripotency and transcription factor Oct4

“…Interestingly, like the regulatory elements in FGF4 enhancer, the Sox-2 enhancer also has an octamer motif that can be regulated by Oct4/Sox-2 synergistically [44]. The stem cell-specific gene Utf1 is regulated through synergistic action of Oct4/Sox-2 [45]. These observations illustrate the versatility of Oct4, acting either as a suppressor of genes responsible for ES cell differentiation or as a transactivator of genes known to retain the pluripotency of ES cells.…”

Novel SOX2 partner-factor domain mutation in a four-generation family

“…20,21 In the lens, SOX2 interacts with the lens-specific factor dEF3, both of which bind to the DC5 enhancer and direct d-crystallin lens-specific gene expression. 20 The interaction between SOX2 and dEF3 is dependent on the conserved B group homology region immediately C-terminal to the HMG domain.…”

Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

“…For example, Oct4 dimerizes with Sox2, and the Oct–Sox interface comprises the POU S of Oct4 and the high‐mobility group (HMG) box domain of Sox2 18, 19, 20, 21. Formation of the Oct4–Sox2 heterodimer is dependent upon the specific DNA element 22.…”