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

Montagner, Sara; Leoni, Cristina; Emming, Stefan; Della Chiara, Giulia; Balestrieri, Chiara; Barozzi, Iros; Piccolo, Viviana; Togher, Susan; Ko, Myunggon; Rao, Anjana; Natoli, Gioacchino; Monticelli, Silvia

doi:10.1016/j.celrep.2016.04.044

Back

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

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.

Language