Tet2 facilitates the derepression of myeloid target genes during CEBPα-Induced transdifferentiation of Pre-B cells

Eric M. Kallin, Javier Rodríguez-Ubreva, Jesper Christensen, Luisa Cimmino, Iannis Aifantis, Kristian Helin, Esteban Ballestar, Thomas Graf

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated. An ideal system to study the role of Tet2 in myelopoeisis is CEBPα-induced transdifferentiation of pre-B cells into macrophages. Here we found that CEBPα binds to upstream regions of Tet2 and that the gene becomes activated. Tet2 knockdowns impaired the upregulation of macrophage markers as well as phagocytic capacity, suggesting that the enzyme is required for both early and late stage myeloid differentiation. A slightly weaker effect was seen in primary cells with a Tet2 ablation. Expression arrays of transdifferentiating cells with Tet2 knockdowns permitted the identification of a small subset of myeloid genes whose upregulation was blunted. Activation of these target genes was accompanied by rapid increases of promoter hydroxy-methylation. Our observations indicate that Tet2 helps CEBPα rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages.

Original languageEnglish (US)
Pages (from-to)266-276
Number of pages11
JournalMolecular Cell
Volume48
Issue number2
DOIs
StatePublished - Oct 26 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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