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Open Access Highly Accessed Research article

Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state

Silvia Parisi12*, Luca Cozzuto1, Carolina Tarantino12, Fabiana Passaro3, Simona Ciriello1, Luigi Aloia12, Dario Antonini12, Vincenzo De Simone3, Lucio Pastore13 and Tommaso Russo13*

Author Affiliations

1 CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 482, 80145 Naples, Italy

2 European School of Molecular Medicine (SEMM), Via Gaetano Salvatore 482, 80145 Naples, Italy

3 Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli "Federico II", Via Sergio Pansini 5, 80131 Naples, Italy

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BMC Biology 2010, 8:128  doi:10.1186/1741-7007-8-128

Published: 27 September 2010

Abstract

Background

A growing body of evidence has shown that Krüppel-like transcription factors play a crucial role in maintaining embryonic stem cell (ESC) pluripotency and in governing ESC fate decisions. Krüppel-like factor 5 (Klf5) appears to play a critical role in these processes, but detailed knowledge of the molecular mechanisms of this function is still not completely addressed.

Results

By combining genome-wide chromatin immunoprecipitation and microarray analysis, we have identified 161 putative primary targets of Klf5 in ESCs. We address three main points: (1) the relevance of the pathways governed by Klf5, demonstrating that suppression or constitutive expression of single Klf5 targets robustly affect the ESC undifferentiated phenotype; (2) the specificity of Klf5 compared to factors belonging to the same family, demonstrating that many Klf5 targets are not regulated by Klf2 and Klf4; and (3) the specificity of Klf5 function in ESCs, demonstrated by the significant differences between Klf5 targets in ESCs compared to adult cells, such as keratinocytes.

Conclusions

Taken together, these results, through the definition of a detailed list of Klf5 transcriptional targets in mouse ESCs, support the important and specific functional role of Klf5 in the maintenance of the undifferentiated ESC phenotype.

See: http://www.biomedcental.com/1741-7007/8/125 webcite