JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency.
Animals
Catalysis
Cell Proliferation
Cellular Reprogramming
Cellular Senescence
Demethylation
Enhancer Elements, Genetic
/ genetics
Epithelial Cells
/ metabolism
Fibroblasts
/ cytology
Gene Expression Regulation, Developmental
Genome
Histones
/ metabolism
Jumonji Domain-Containing Histone Demethylases
/ metabolism
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
/ metabolism
Lysine
/ metabolism
Mice
Models, Biological
Pluripotent Stem Cells
/ cytology
Promoter Regions, Genetic
Transcriptional Activation
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 10 2020
08 10 2020
Historique:
received:
22
07
2019
accepted:
16
09
2020
entrez:
9
10
2020
pubmed:
10
10
2020
medline:
21
10
2020
Statut:
epublish
Résumé
The interplay between the Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and transcriptional/epigenetic co-regulators in somatic cell reprogramming is incompletely understood. Here, we demonstrate that the histone H3 lysine 27 trimethylation (H3K27me3) demethylase JMJD3 plays conflicting roles in mouse reprogramming. On one side, JMJD3 induces the pro-senescence factor Ink4a and degrades the pluripotency regulator PHF20 in a reprogramming factor-independent manner. On the other side, JMJD3 is specifically recruited by KLF4 to reduce H3K27me3 at both enhancers and promoters of epithelial and pluripotency genes. JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL and ultimately transcriptional elongation. This competition of forces can be shifted towards improved reprogramming by using early passage fibroblasts or boosting JMJD3's catalytic activity with vitamin C. Our work, thus, establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription.
Identifiants
pubmed: 33033262
doi: 10.1038/s41467-020-18900-z
pii: 10.1038/s41467-020-18900-z
pmc: PMC7545202
doi:
Substances chimiques
Histones
0
Klf4 protein, mouse
0
Kruppel-Like Factor 4
0
Kruppel-Like Transcription Factors
0
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
Kdm6b protein, mouse
EC 1.5.-
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5061Références
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