Tet2 facilitates the derepression of myeloid target genes during CEBPα-induced transdifferentiation of pre-B cells
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning
Standard
Tet2 facilitates the derepression of myeloid target genes during CEBPα-induced transdifferentiation of pre-B cells. / Kallin, Eric M; Rodríguez-Ubreva, Javier; Christensen, Jesper Aagaard; Cimmino, Luisa; Aifantis, Iannis; Helin, Kristian; Ballestar, Esteban; Graf, Thomas.
I: Molecular Cell, Bind 48, Nr. 2, 26.10.2012, s. 266-76.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Tet2 facilitates the derepression of myeloid target genes during CEBPα-induced transdifferentiation of pre-B cells
AU - Kallin, Eric M
AU - Rodríguez-Ubreva, Javier
AU - Christensen, Jesper Aagaard
AU - Cimmino, Luisa
AU - Aifantis, Iannis
AU - Helin, Kristian
AU - Ballestar, Esteban
AU - Graf, Thomas
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/10/26
Y1 - 2012/10/26
N2 - 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.
AB - 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.
KW - Azacitidine
KW - CCAAT-Enhancer-Binding Proteins
KW - Cell Differentiation
KW - Cell Line
KW - Cell Transdifferentiation
KW - DNA-Binding Proteins
KW - Gene Expression Regulation, Developmental
KW - Gene Knockdown Techniques
KW - Hematopoietic Stem Cells
KW - Humans
KW - Macrophages
KW - Myeloid Cells
KW - Myelopoiesis
KW - Precursor Cells, B-Lymphoid
KW - Proto-Oncogene Proteins
U2 - 10.1016/j.molcel.2012.08.007
DO - 10.1016/j.molcel.2012.08.007
M3 - Journal article
C2 - 22981865
VL - 48
SP - 266
EP - 276
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -
ID: 94395448