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Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
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Number of Authors: 72019 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 381, no 1, p. 129-138Article in journal (Refereed) Published
Abstract [en]

Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role for Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at gene regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interacts with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but could rather regulate other processes in the nucleoplasm.

Place, publisher, year, edition, pages
2019. Vol. 381, no 1, p. 129-138
Keywords [en]
Sox2, 7SK, Non-coding RNA, Pluripotency, RNA binding protein, Chromatin, SILAC, Quantitative proteomics, ChIRP, RNA immunoprecipitation
National Category
Biological Sciences Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:su:diva-170064DOI: 10.1016/j.yexcr.2019.05.006ISI: 000470051500015PubMedID: 31077711OAI: oai:DiVA.org:su-170064DiVA, id: diva2:1335807
Available from: 2019-07-08 Created: 2019-07-08 Last updated: 2019-07-08Bibliographically approved

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Engström, Pär G.Castelo-Branco, Gonçalo
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Department of Biochemistry and BiophysicsScience for Life Laboratory (SciLifeLab)
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Experimental Cell Research
Biological SciencesMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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