Differential regulation of the Oct-3/4 gene in cell culture model systems that parallel different stages of mammalian development

Molecular Reproduction and Development
Sunil Kumar MallannaA Rizzino

Abstract

Oct-3/4 is an essential transcription factor that regulates stem cell fate during embryogenesis. Previous reports have shown that the Oct-3/4 gene utilizes different enhancers to regulate its expression as development proceeds. However, the cis-elements contributing to the differential activity of these enhancers require further study. Here, we investigated the function of the HMG/POU cassette and LRH-1 site present in the distal enhancer (DE) and the proximal enhancer, respectively. F9 and P19 EC cells were the focus of this study because their differential utilization of Oct-3/4 enhancers parallels the use of these enhancers during different stages of development. We determined that the LRH-1 site functions as a positive and a negative cis-regulatory element in P19 and F9 EC cells, respectively. Furthermore, we determined that the HMG/POU cassette in the DE strongly activates the Oct-3/4 promoter in F9 cells, but is a much weaker positive regulatory element in P19 cells. Given that HMG/POU cassettes play key roles in the regulation of at least seven essential genes, the Oct-3/4 HMG/POU cassette was examined more closely by focusing on Sox2, which can bind to HMG/POU cassettes. Although chromatin immunoprecipitation demonstrat...Continue Reading

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Citations

Sep 30, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Harini ChakravarthyAngie Rizzino
Dec 18, 2009·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Angie Rizzino
Apr 5, 2017·Stem Cells International·Gregory M Kelly, Mohamed I Gatie

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