Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated
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RESEARCH ARTICLE
Open Access
Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state Silvia Parisi1,2*, Luca Cozzuto1, Carolina Tarantino1,2, Fabiana Passaro3, Simona Ciriello1, Luigi Aloia1,2, Dario Antonini1,2, Vincenzo De Simone3, Lucio Pastore1,3, Tommaso Russo1,3*
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
Background Embryonic stem cells (ESCs) are derived from the inner cell mass of preimplantation embryos; they are amenable to manipulation, enrichment and expansion and retain the developmental potency of embryonic founder cells, being able to differentiate into cells and tissues of all three germ layers both in vitro and in vivo [1,2]. For these characteristics, ESCs represent an invaluable source of different cell types, thus opening up new possibilities for cell therapy. The understanding of the transcriptional regulatory networks that operate in ESCs is fundamental to unravel the molecular basis of pluripotency, self-renewal and reprogramming. The complexity of this regulatory network was highlighted by the * Correspondence: [email protected]; [email protected] 1 CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 482, 80145 Naples, Italy Full list of author information is available at the end of the article
identification of hundreds of genes, targets of the ESC master genes Oct3/4, Nanog and Sox2 [3,4]. In addition to these master regulatory factors, several other transcription factors play important roles in the control of this regulatory network [5-9], such as Krüppel-like factors (Klfs). Klfs belong to the Sp1 family of transcription factors with over 20 members [10,11]. Three members of this family (K
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