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Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms4719

2041-1723

Irène Aksoy, Vincent Giudice, Edwige Delahaye, Florence Wianny, Maxime Aubry, Magali Mure, Jiaxuan Chen, Ralf Jauch, Gireesh K. Bogu, Tobias Nolden, Heinz Himmelbauer, Michael Xavier Doss, Agapios Sachinidis, Herbert Schulz, Oliver Hummel, Paola Martinelli, Norbert Hübner, Lawrence W. Stanton, Francisco X. Real, Pierre-Yves Bourillot, Pierre Savatier,

Epigenetics and DNA Methylation

Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells. The Krüppel-like factors Klf4 and Klf5 have wide roles in cell biology including the regulation of pluripotency. In this study, Aksoy et al. demonstrate that Klf4 preferentially blocks the expression of endodermal markers in embryonic stem cells, whereas Klf5 negatively regulates mesodermal factors.