| Literature DB >> 24770696 |
Irène Aksoy1, Vincent Giudice2, Edwige Delahaye3, Florence Wianny3, Maxime Aubry3, Magali Mure3, Jiaxuan Chen4, Ralf Jauch5, Gireesh K Bogu4, Tobias Nolden6, Heinz Himmelbauer7, Michael Xavier Doss8, Agapios Sachinidis9, Herbert Schulz10, Oliver Hummel10, Paola Martinelli11, Norbert Hübner10, Lawrence W Stanton4, Francisco X Real12, Pierre-Yves Bourillot3, Pierre Savatier3.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 24770696 DOI： 10.1038/ncomms4719
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919