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JNK ‐dependent gene regulatory circuitry governs mesenchymal fate
Author(s) -
Sahu Sanjeeb Kumar,
Garding Angela,
Tiwari Neha,
Thakurela Sudhir,
Toedling Joern,
Gebhard Susanne,
Ortega Felipe,
Schmarowski Nikolai,
Berninger Benedikt,
Nitsch Robert,
Schmidt Marcus,
Tiwari Vijay K
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490693
Subject(s) - biology , reprogramming , transcription factor , mesenchymal stem cell , epithelial–mesenchymal transition , microbiology and biotechnology , chromatin , neural crest , transcriptome , effector , regulation of gene expression , cancer cell , gene , genetics , gene expression , cancer , downregulation and upregulation , embryo
The epithelial to mesenchymal transition ( EMT ) is a biological process in which cells lose cell–cell contacts and become motile. EMT is used during development, for example, in triggering neural crest migration, and in cancer metastasis. Despite progress, the dynamics of JNK signaling, its role in genomewide transcriptional reprogramming, and involved downstream effectors during EMT remain largely unknown. Here, we show that JNK is not required for initiation, but progression of phenotypic changes associated with EMT . Such dependency resulted from JNK ‐driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we identified eight novel JNK ‐induced transcription factors that were required for proper EMT . Three of these factors were also highly expressed in invasive cancer cells where they function in gene regulation to maintain mesenchymal identity. These factors were also induced during neuronal development and function in neuronal migration in vivo . These comprehensive findings uncovered a kinetically distinct role for the JNK pathway in defining the transcriptome that underlies mesenchymal identity and revealed novel transcription factors that mediate these responses during development and disease.