Publication: ChIP-Seq and RNA-Seq Analyses Identify Components of the Wnt and Fgf
Signaling Pathways as Prep1 Target Genes in Mouse Embryonic Stem Cells
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2015
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Public Library of Science (PLOS)
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Abstract
The Prep1 (Pknox1) homeodomain transcription factor is essential at
multiple stages of embryo development. In the E11.5 embryo trunk, we
previously estimated that Prep1 binds about 3,300 genomic sites at a
highly specific decameric consensus sequence, mainly governing basal
cellular functions. We now show that in embryonic stem (ES) cells Prep1
binding pattern only partly overlaps that of the embryo trunk, with
about 2,000 novel sites. Moreover, in ES cells Prep1 still binds mostly
to promoters, as in total embryo trunk but, among the peaks bound
exclusively in ES cells, the percentage of enhancers was threefold
higher. RNA-seq identifies about 1800 genes down-regulated in Prep1(-/-)
ES cells which belong to gene ontology categories not enriched in the
E11.5 Prep1(i/i) differentiated embryo, including in particular
essential components of the Wnt and Fgf pathways. These data agree with
aberrant Wnt and Fgf expression levels in the Prep1(-/-) ES cells with a
deficient embryoid bodies (EBs) formation and differentiation.
Re-establishment of the Prep1 level rescues the phenotype.
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PLoS One. 2015; 10(4):e0122518