Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2.
cell state transition
cellular plasticity
differentiation
pluripotency
reprogramming
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
03
06
2019
revised:
21
10
2019
accepted:
24
10
2019
pubmed:
30
11
2019
medline:
14
7
2020
entrez:
30
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31782544
doi: 10.15252/embj.2019102591
pmc: PMC6960450
mid: EMS85790
doi:
Substances chimiques
Chromatin
0
Transcription Factors
0
Zfp281 protein, mouse
0
Zic2 protein, mouse
0
GLP protein, mouse
EC 2.1.1.43
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Banques de données
GEO
['GSE131017']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e102591Subventions
Organisme : Medical Research Council
ID : G1100526
Pays : United Kingdom
Organisme : EU Seventh Framework Programme Integrated Project SyBoSS
Pays : International
Organisme : Novartis Research Foundation
Pays : International
Informations de copyright
© 2019 Friedrich Miescher Institute for Biomedical Research.
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