Novel Variant of OCT4, Named OCT4B5, is Highly Expressed in Human Pluripotent Cells
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Novel Variant of OCT4, Named OCT4B5, is Highly Expressed in Human Pluripotent Cells Majid Mehravar 1 & Ensieh M. Poursani 1,2 Accepted: 19 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Alternative promoter and alternative splicing are two important mechanisms of gene regulation and protein diversity in different physiological contexts of eukaryotes, especially in stem cells and developmental stages. Pou5f1 gene which codes the stemness marker OCT4, utilizes alternative splicing and promoter mechanisms, which result in generation of multiple spliced variants and subsequently multiple protein isoforms. By far, nine variants of OCT4 (OCT4A, OCT4B, OCT4B1, OCT4B2, OCT4B3, OCT4B4, OCT4C, OCT4C1, and OCT4D) have been introduced. It has been well established that OCT4A plays essential roles in early developmental stages as well as maintenance of stemness in embryonic stem cells (ESCs). However, the roles and functions of other variants and isoforms of OCT4 in biological systems are less appreciated. In this study, we report a new OCT4 variant, designated as OCT4B5. RT-PCR assay on different human cell lines including pluripotent, normal and cancer cells showed that OCT4B5 is expressed at variable level in different cell lines. By semi-quantifying of OCT4B5 expression in pluripotent and differentiated states of NT2 cell lines, we reveal that this variant of OCT4 is highly expressed in undifferentiated state and its expression is down-regulated upon differentiation. Compared to OCT4A which is sharply down-regulated in retinoic acid induced differentiation of NT2 cell line, the expression of OCT4B5 remains at low level in differentiated state. Overall, this study emphasizes the complexity of OCT4 gene expression and regulation in different states of stem cells and physiological contexts. Keywords Pou5f1, OCT4 . OCT4A . OCT4B5 . Alternative splicing . Alternative promoter . Pluripotent cells . Cancer cell lines . Stem cells
Introduction Alternative splicing (AS) and alternative promoter (AP) mechanisms of gene regulation enable eukaryotic cells to diversify their gene products from limited number of genes. OCT4 is a crucial factor in maintaining self-renewal and pluripotency in embryonic stem (ES) and embryonic carcinoma (EC) cells which is encoded by Pou5f1 gene [1]. Based on expressed sequence tag (EST) data, four transcription start sites have been assigned for OCT4 gene, showing four independent promoters (alternative promoter) that function upstream of different transcription start sites (TSSs) resulting in
* Ensieh M. Poursani [email protected] 1
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2
Hematology/Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
four categories of OCT4 variants (variant A, B, C, and D). In addition, alternative splicing mechanism more diversifies OCT4 variants. So far, nine different transcripts have been assigned for
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