Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells
ABSTRACT The Sox2 transcription factor is expressed early in the stem cells of the blastocyst inner cell mass and, later, in neural stem cells. We previously identified a Sox2 5'-regulatory region directing transgene expression to the inner cell mass and, later, to neural stem cells and precursors of the forebrain. Here, we identify a core enhancer element able to specify transgene expression in forebrain neural precursors of mouse embryos, and we show that the same core element efficiently activates transcription in inner cell mass-derived embryonic stem (ES) cells. Mutation of POU factor binding sites, able to recognize the neural factors Brn1 and Brn2, shows that these sites contribute to transgene activity in neural cells. The same sites are also essential for activity in ES cells, where they bind different members of the POU family, including Oct4, as shown by gel shift assays and chromatin immunoprecipitation with anti-Oct4 antibodies. Our findings indicate a role for the same POU binding motifs in Sox2 transgene regulation in both ES and neural precursor cells. Oct4 might play a role in the regulation of Sox2 in ES (inner cell mass) cells and, possibly, at the transition between inner cell mass and neural cells, before recruitment of neural POU factors such as Brn1 and Brn2.
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ABSTRACT: Linc-POU3F3 levels were extraordinarily associated with the tumor WHO grade.•Linc-POU3F3 and POU3F3 have reverse correlated with expression in glioma.•Linc-POU3F3 affects colony formation and cell proliferation of glioma cells.•Linc-POU3F3 could serve as a position marker, recruiting regulators to target gene.Gene 01/2015; 554(1). DOI:10.1016/j.gene.2014.10.038 · 2.08 Impact Factor
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ABSTRACT: The transcription factor Sox2 plays a central role in the regulation of neuro-sensory development, and many other developmental processes. To gain an in depth understanding of the Sox2 gene regulation, we previously investigated the Sox2-proximal 50-kb region of the chicken genome to determine enhancers based on functional assays using chicken embryo electroporation. We identified 11 enhancers with specificity for neuro-sensory tissues. In this study, we extended the analysis of Sox2 locus-associated enhancers to a 200-kb region and identified 16 additional enhancers with functions in neuro-sensory development. These enhancers roughly correspond to a fraction of the sequence blocks that are highly conserved between chicken and mammalian genomes. The neural enhancers were activated in sequence, thereby creating a complex pattern of functional overlaps in the developing central nervous system (CNS). The variations in the specificities of the sensory enhancers also reflected the intermediate steps of sensory tissue development. This study provides an example where a single transcription factor gene has numerous regulatory elements that allow it to fulfill many functional roles in different biological contexts. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.Embryologia 11/2014; 57(1). DOI:10.1111/dgd.12185 · 2.18 Impact Factor