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  ChIP-Seq and RNA-Seq Analyses Identify Components of the Wnt and Fgf Signaling Pathways as Prep1 Target Genes in Mouse Embryonic Stem Cells

Laurent, A., Calabrese, M., Warnatz, H. J., Yaspo-Lehrach, M.-L., Tkachuk, V., Torres, M., et al. (2015). ChIP-Seq and RNA-Seq Analyses Identify Components of the Wnt and Fgf Signaling Pathways as Prep1 Target Genes in Mouse Embryonic Stem Cells. PLoS One. doi:10.1371/journal.pone.0122518.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002D-436E-C Version Permalink: https://hdl.handle.net/11858/00-001M-0000-002D-436F-A
Genre: Journal Article

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2015-04-01
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Laurent, Audrey1, Author
Calabrese, Manuela1, Author
Warnatz, Hans Jörg2, Author           
Yaspo-Lehrach, Marie-Laure3, Author           
Tkachuk, Vsevolod4, Author
Torres, Miguel5, Author
Blasi, Francesco1, Author
Penkov, Dimitry1, 6, Author
Affiliations:
1IFOM (FIRC Institute of Molecular Oncology), IFOM-IEO-Campus , Milan, Italy , ou_persistent22              
2Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497699              
3Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              
4 Faculty of Basic Medicine, Lomonosov Moscow State University, Moscow, Russia , ou_persistent22              
5Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain , ou_persistent22              
6 Department of Experimental Cardiology, Russian Cardiology Research and Production Complex , Moscow, Russia , ou_persistent22              

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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 three-fold 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 Prep1i/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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Language(s): eng - English
 Dates: 2015-04-13
 Publication Status: Published online
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 Identifiers: DOI: 10.1371/journal.pone.0122518
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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850