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  Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors

Orgeur, M., Martens, M., Leonte, G., Nassari, S., Bonnin, M.-A., Börno, S. T., et al. (2018). Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors. Development, 145(7): dev161208. doi:10.1242/dev.161208.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-E315-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-5AD0-C
Genre: Journal Article

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 Creators:
Orgeur, Mickael , Author
Martens, Marvin , Author
Leonte, Georgeta , Author
Nassari, Sonya , Author
Bonnin, Marie-Ange , Author
Börno, Stefan T.1, Author              
Timmermann, Bernd1, Author              
Hecht, Jochen, Author
Duprez, Delphine , Author
Stricker, Sigmar2, Author              
Affiliations:
1Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: Chicken model; Connective tissue differentiation; Extracellular matrix; Limb development; Signalling pathways; Transcription factors; Transcriptional regulatory network
 Abstract: Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling revealed a set of common genes regulated by all five transcription factors, which we propose as connective tissue core expression set. This common core was enriched in genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created via the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development.

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Language(s): eng - English
 Dates: 2018-02-242018-03-29
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1242/dev.161208
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Title: Development
  Other : Development
Source Genre: Journal
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Publ. Info: Cambridge, Cambridgeshire : Company of Biologists
Pages: - Volume / Issue: 145 (7) Sequence Number: dev161208 Start / End Page: - Identifier: ISSN: 0950-1991
PII: dev.161208
CoNE: /journals/resource/954927546241