TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1566-1579
Number of pages14
JournalCell Reports
Volume15
Issue number7
DOIs
Publication statusPublished - May 17 2016

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Keywords

  • Differentiation
  • DNA hydroxymethylation
  • Epigenetics
  • Mast cells
  • Proliferation
  • TET

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Montagner, S., Leoni, C., Emming, S., Della Chiara, G., Balestrieri, C., Barozzi, I., Piccolo, V., Togher, S., Ko, M., Rao, A., Natoli, G., & Monticelli, S. (2016). TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities. Cell Reports, 15(7), 1566-1579. https://doi.org/10.1016/j.celrep.2016.04.044