Targeted alternative splicing of TAF4: a new strategy for cell reprogramming.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Cellular Reprogramming*; TATA-Binding Protein Associated Factors/*metabolism ; Transcription Factor TFIID/*metabolism; Alternative Splicing ; Cadherins/metabolism ; Cell Differentiation ; Cell Line ; Cell Movement ; Dermis/cytology ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Melanocytes/cytology ; Melanocytes/metabolism ; Microphthalmia-Associated Transcription Factor/metabolism ; Microscopy, Fluorescence ; Neoplastic Stem Cells/cytology ; Neoplastic Stem Cells/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; TATA-Binding Protein Associated Factors/antagonists & inhibitors ; TATA-Binding Protein Associated Factors/genetics ; Transcription Factor TFIID/antagonists & inhibitors ; Transcription Factor TFIID/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism
    • Abstract:
      Reprogramming of somatic cells has become a versatile tool for biomedical research and for regenerative medicine. In the current study, we show that manipulating alternative splicing (AS) is a highly potent strategy to produce cells for therapeutic applications. We demonstrate that silencing of hTAF4-TAFH activity of TAF4 converts human facial dermal fibroblasts to melanocyte-like (iMel) cells. iMel cells produce melanin and express microphthalmia-associated transcription factor (MITF) and its target genes at levels comparable to normal melanocytes. Reprogramming of melanoma cells by manipulation with hTAF4-TAFH activity upon TAFH RNAi enforces cell differentiation towards chondrogenic pathway, whereas ectoptic expression of TAF4 results in enhanced multipotency and neural crest-like features in melanoma cells. In both cell states, iMels and cancer cells, hTAF4-TAFH activity controls migration by supporting E- to N-cadherin switches. From our data, we conclude that targeted splicing of hTAF4-TAFH coordinates AS of other TFIID subunits, underscoring the role of TAF4 in synchronised changes of Pol II complex composition essential for efficient cellular reprogramming. Taken together, targeted AS of TAF4 provides a unique strategy for generation of iMels and recapitulating stages of melanoma progression.
    • References:
      Nature. 2013 Jan 31;493(7434):699-702. (PMID: 23292512)
      Nature. 2010 Nov 11;468(7321):316-20. (PMID: 20953172)
      Mol Cell. 2001 Sep;8(3):591-600. (PMID: 11583621)
      Pigment Cell Melanoma Res. 2008 Feb;21(1):39-55. (PMID: 18353142)
      Genes Dev. 2007 Sep 1;21(17):2137-49. (PMID: 17704303)
      J Mol Neurosci. 2015 Jan;55(1):160-6. (PMID: 24696168)
      Stem Cells. 2006 Dec;24(12):2685-91. (PMID: 16916925)
      Mol Cell. 2003 Oct;12(4):991-1001. (PMID: 14580349)
      Mol Ther. 2013 Jun;21(6):1242-50. (PMID: 23568261)
      Curr Opin Genet Dev. 2010 Oct;20(5):533-40. (PMID: 20598874)
      Cell. 2011 Sep 2;146(5):720-31. (PMID: 21884934)
      Annu Rev Biochem. 1996;65:769-99. (PMID: 8811195)
      Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3906-11. (PMID: 21368148)
      Mol Cell Neurosci. 2005 Jun;29(2):250-8. (PMID: 15911349)
      Cell. 2011 Sep 30;147(1):132-46. (PMID: 21924763)
      Development. 2007 Aug;134(16):2947-58. (PMID: 17626060)
      Int J Surg Pathol. 2012 Apr;20(2):169-72. (PMID: 22334614)
      Curr Protoc Cell Biol. 2001 May;Chapter 2:Unit 2.1. (PMID: 18228346)
      Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5229-33. (PMID: 12702775)
      PLoS One. 2008 Jul 16;3(7):e2721. (PMID: 18628956)
      Nature. 2013 Jun 13;498(7453):176-7. (PMID: 23739330)
      Cell. 2007 Mar 9;128(5):853-64. (PMID: 17350573)
      Stem Cells Dev. 2011 Aug;20(8):1327-36. (PMID: 21142453)
      Cancer Res. 1988 Dec 1;48(23):6933-7. (PMID: 3180101)
      Nat Neurosci. 2007 Dec;10(12):1519-28. (PMID: 17994014)
      Cell. 2008 Jun 13;133(6):1106-17. (PMID: 18555785)
      Elife. 2012 Nov 13;1:e00068. (PMID: 23150797)
      Biochem Biophys Res Commun. 2004 Dec 10;325(2):574-9. (PMID: 15530431)
      Stem Cells. 2014 Feb;32(2):349-63. (PMID: 23765875)
      J Cutan Pathol. 2001 Oct;28(9):482-5. (PMID: 11553315)
      Cell. 2010 Aug 6;142(3):375-86. (PMID: 20691899)
      Int J Mol Sci. 2014 Sep 19;15(9):16680-97. (PMID: 25244017)
      Int J Cancer. 2000 Feb 15;85(4):492-7. (PMID: 10699920)
      Cell. 2006 Aug 25;126(4):663-76. (PMID: 16904174)
      Nat Genet. 2006 Apr;38(4):431-40. (PMID: 16518401)
      Genes Cells. 2013 Mar;18(3):225-37. (PMID: 23350932)
      Oncogene. 2008 Jan 17;27(4):477-89. (PMID: 17637747)
      Curr Opin Genet Dev. 2003 Oct;13(5):529-36. (PMID: 14550420)
      Nature. 2010 Feb 25;463(7284):1035-41. (PMID: 20107439)
      BMC Mol Biol. 2001;2:4. (PMID: 11285139)
      Cancer Res. 1985 Apr;45(4):1474-8. (PMID: 2983883)
      Genes Dev. 2010 Nov 1;24(21):2343-64. (PMID: 21041405)
      Exp Dermatol. 2014 Jan;23(1):18-9. (PMID: 24372649)
      Genes Dev. 2011 Apr 1;25(7):701-16. (PMID: 21460037)
      Funct Integr Genomics. 2002 Aug;2(3):105-19. (PMID: 12185458)
      Cell. 2014 Feb 13;156(4):663-77. (PMID: 24529372)
      Nature. 2013 Mar 28;495(7442):516-9. (PMID: 23503660)
      EMBO Rep. 2014 Mar;15(3):244-53. (PMID: 24531722)
      J Biol Chem. 2009 Feb 13;284(7):4343-53. (PMID: 19098008)
      Nat Rev Genet. 2010 Aug;11(8):549-58. (PMID: 20628347)
      Proteomics. 2011 Jun;11(11):2275-82. (PMID: 21548097)
      Nat Commun. 2016 Mar 30;7:11063. (PMID: 27026076)
      Cancer Lett. 2013 Sep 10;338(1):74-81. (PMID: 23073475)
      Front Oncol. 2014 Mar 11;4:45. (PMID: 24653979)
      Trends Mol Med. 2012 May;18(5):245-7. (PMID: 22521522)
      Curr Stem Cell Res Ther. 2012 Nov;7(6):400-6. (PMID: 22953724)
      Cancer Cell. 2010 Nov 16;18(5):510-23. (PMID: 21075313)
      EMBO J. 2005 Aug 3;24(15):2753-67. (PMID: 16015375)
      Cell. 1987 Dec 24;51(6):987-1000. (PMID: 3690668)
      Pigment Cell Melanoma Res. 2012 Sep;25(5):573-83. (PMID: 22681858)
      Nat Commun. 2014 Dec 16;5:5807. (PMID: 25510211)
      J Nucleic Acids. 2012;2012:269570. (PMID: 22132318)
      Nature. 2011 May 11;475(7356):386-9. (PMID: 21562492)
      Genes Dev. 2002 Mar 15;16(6):673-5. (PMID: 11963920)
      Mol Cell. 2009 Dec 25;36(6):924-31. (PMID: 20064459)
      Cell Stem Cell. 2011 Dec 2;9(6):504-16. (PMID: 22136926)
      Nature. 2013 Jun 13;498(7453):241-5. (PMID: 23739326)
      PLoS One. 2013 Oct 02;8(10):e74799. (PMID: 24098348)
      Nat Rev Cancer. 2014 Aug;14(8):568-73. (PMID: 25030952)
      Methods Mol Biol. 2013;997:23-33. (PMID: 23546745)
      Nat Rev Cancer. 2002 Jun;2(6):442-54. (PMID: 12189386)
    • Accession Number:
      0 (Cadherins)
      0 (Microphthalmia-Associated Transcription Factor)
      0 (RNA, Small Interfering)
      0 (TAF4 protein, human)
      0 (TATA-Binding Protein Associated Factors)
      0 (Transcription Factor TFIID)
      0 (Transcription Factors)
    • Publication Date:
      Date Created: 20160809 Date Completed: 20180423 Latest Revision: 20181113
    • Publication Date:
      20240829
    • Accession Number:
      PMC4976350
    • Accession Number:
      10.1038/srep30852
    • Accession Number:
      27499390