Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state.
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.
Parisi
Silvia
S
CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 482, 80145 Naples, Italy. parisi@ceinge.unina.it
Cozzuto
Luca
L
Tarantino
Carolina
C
Passaro
Fabiana
F
Ciriello
Simona
S
Aloia
Luigi
L
Antonini
Dario
D
De Simone
Vincenzo
V
Pastore
Lucio
L
Russo
Tommaso
T
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
C000715468:Klf4 protein, mouse; C118391:Klf5 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016601:RNA-Binding Proteins; C532831:SERBP1 protein, mouse