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Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2.
- Source :
-
The EMBO journal [EMBO J] 2020 Jan 15; Vol. 39 (2), pp. e102591. Date of Electronic Publication: 2019 Nov 29. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2019 Friedrich Miescher Institute for Biomedical Research.)
- Subjects :
- Animals
Cells, Cultured
Chromatin chemistry
Chromatin metabolism
Mice
Mouse Embryonic Stem Cells metabolism
Pluripotent Stem Cells metabolism
Cell Differentiation
Gene Expression Regulation
Histone-Lysine N-Methyltransferase metabolism
Mouse Embryonic Stem Cells cytology
Pluripotent Stem Cells cytology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 39
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 31782544
- Full Text :
- https://doi.org/10.15252/embj.2019102591