Journal article

TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities

  • Montagner, Sara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland
  • Leoni, Cristina Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland
  • Emming, Stefan Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland
  • Della Chiara, Giulia Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy
  • Balestrieri, Chiara Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy
  • Barozzi, Iros Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy
  • Piccolo, Viviana Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy
  • Togher, Susan La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
  • Ko, Myunggon La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA - School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulju-gun, Ulsan 689-798, Republic of Korea
  • Rao, Anjana La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
  • Natoli, Gioacchino Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy
  • Monticelli, Silvia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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    17.05.2016
Published in:
  • Cell reports. - 2016, vol. 15, no. 7, p. 1566-1579
English Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC). Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of downregulated genes. Impaired differentiation of Tet2- ablated cells could be relieved or further exacerbated by modulating the activity of other TET family members, and mechanistically it could be linked to the dysregulated expression of C/EBP family transcription factors. Conversely, the marked increase in proliferation induced by the loss of TET2 could be rescued exclusively by re-expression of wild-type or catalytically inactive TET2. Our data indicate that, in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/319146
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