Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2.
- Mayer D Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Stadler MB Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Rittirsch M Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Hess D Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Lukonin I Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- Winzi M Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
- Smith A Wellcome-MRC Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK.
- Buchholz F Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
- Betschinger J Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
- 2019-11-30
Published in:
- The EMBO journal. - 2020
cell state transition
cellular plasticity
differentiation
pluripotency
reprogramming
Animals
Cell Differentiation
Cells, Cultured
Chromatin
Gene Expression Regulation
Histone-Lysine N-Methyltransferase
Mice
Mouse Embryonic Stem Cells
Pluripotent Stem Cells
Transcription Factors
English
Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bidirectional regulator of cell state interconversion. We showed that subtle chromatin binding changes in differentiated cells translate into activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and stabilization of the zinc finger TF Zic2 at enhancers and promoters. Genetic gain-of-function and loss-of-function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state and in restricting reprogramming of EpiSCs. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity.
- Language
-
- English
- Open access status
- green
- Identifiers
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- DOI 10.15252/embj.2019102591
- PMID 31782544
- Persistent URL
- https://sonar.ch/global/documents/238254
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