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 2016-05-17 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. application/pdf https://susi.usi.ch/global/documents/319146 https://n2t.net/ark:/12658/srd1319146 https://susi.usi.ch/documents/319146/files/Montagner_CR_2016.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.04.044 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319146 info:eu-repo/semantics/openAccess CC BY-NC-ND Cell reports. - 2016, vol. 15, no. 7, p. 1566-1579 Differentiation DNA hydroxymethylation Epigenetics Mast cells Proliferation TET info:eu-repo/classification/udc/61 TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities http://purl.org/coar/resource_type/c_6501