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Differential Roles ofSall4 Isoforms inEmbryonic Stem CellPluripotency Sridhar RaoZhen ShaoS. A. Roumiantsev2010 год

Differential Roles of Sall4 Isoforms in Embryonic Stem Cell Pluripotency
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Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: AbstractMurine embryonic stem (ES) cells are defined by continuous self-renewal and pluripotency. A diverse repertoire of protein isoforms arising from alternative splicing is expressed in ES cells without defined biological roles. Sall4, a transcription factor essential for pluripotency, exists as two isoforms (Sall4a and Sall4b). Both isoforms can form homodimers and a heterodimer with each other, and each can interact with Nanog. By genomewide location analysis, we determined that Sall4a and Sall4b have overlapping, but not identical binding sites within the ES cell genome. In addition, Sall4b, but not Sall4a, binds preferentially to highly expressed loci in ES cells. Sall4a and Sall4b binding sites are distinguished by both epigenetic marks at target loci and their clustering with binding sites of other pluripotency factors. When ES cells expressing a single isoform of Sall4 are generated, Sall4b alone could maintain the pluripotent state, although it could not completely suppress all differentiation markers. Sall4a and Sall4b collaborate in maintenance of the pluripotent state but play distinct roles. Our work is novel in establishing such isoform-specific differences in ES cells. S.R. is funded by a Career Development Award from the NHLBI (5K08HL87951). S.H.O. is an investigator of the HHMI. G.Y. is supported by a Claudia Adams Barr Award.We thank Xiaohua Shen and Jonathan Snow for helpful discussions during preparation of the manuscript. We thank W. Hahn for supplying the empty lentiviral vector pLKO.1 and I. Chambers and A. Smith for providing the pPyCAG vectors used in this study.Supplemental material for this article may be found at http://mcb.asm.org/.
Год издания: 2010
Авторы: Sridhar Rao, Zhen Shao, S. A. Roumiantsev, Lindsay T. McDonald, Guo‐Cheng Yuan, Stuart H. Orkin
Издательство: Taylor & Francis
Источник: Molecular and Cellular Biology
Ключевые слова: Pluripotent Stem Cells Research, CRISPR and Genetic Engineering, Renal and related cancers
Другие ссылки: Molecular and Cellular Biology (HTML)
Europe PMC (PubMed Central) (PDF)
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PubMed Central (HTML)
CiteSeer X (The Pennsylvania State University) (PDF)
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