AI Article Synopsis

  • The ERK5 MAP kinase signaling pathway is crucial for controlling the expression of genes related to naïve pluripotency in mouse embryonic stem cells (mESCs).
  • Researchers used proteomic profiling to discover that ERK5 also influences genes from the early embryonic 2-cell stage (2C), notably the rejuvenation factor ZSCAN4.
  • ERK5 enhances ZSCAN4 expression and telomere length through the KLF2 transcription factor, but it simultaneously regulates KLF2 levels to prevent overexpression of 2C genes, establishing a feedback loop.

Article Abstract

The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This reveals a function for ERK5 signalling in regulating dynamically expressed early embryonic 2-cell stage (2C) genes including the mESC rejuvenation factor ZSCAN4. ERK5 signalling and ZSCAN4 induction in mESCs increases telomere length, a key rejuvenative process required for prolonged culture. Mechanistically, ERK5 promotes ZSCAN4 and 2C gene expression via transcription of the KLF2 pluripotency transcription factor. Surprisingly, ERK5 also directly phosphorylates KLF2 to drive ubiquitin-dependent degradation, encoding negative feedback regulation of 2C gene expression. In summary, our data identify a regulatory module whereby ERK5 kinase and transcriptional activities bi-directionally control KLF2 levels to pattern 2C gene transcription and a key mESC rejuvenation process.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718266PMC
http://dx.doi.org/10.1042/BCJ20210646DOI Listing

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