KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks.
Animals
Cells, Cultured
Cellular Reprogramming
/ genetics
Chromatin Assembly and Disassembly
/ genetics
Enhancer Elements, Genetic
Female
HEK293 Cells
Humans
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
/ metabolism
Male
Mice
Mouse Embryonic Stem Cells
/ metabolism
Pluripotent Stem Cells
/ metabolism
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
20
07
2018
accepted:
16
08
2019
pubmed:
25
9
2019
medline:
26
11
2019
entrez:
25
9
2019
Statut:
ppublish
Résumé
Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors, as is exemplified by reprogramming somatic cells to pluripotent stem cells through the expression of OCT4, KLF4, SOX2 and cMYC. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood. Here, using KLF4 as a paradigm, we provide a transcription-factor-centric view of chromatin reorganization and its association with three-dimensional enhancer rewiring and transcriptional changes during the reprogramming of mouse embryonic fibroblasts to pluripotent stem cells. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in enhancer connectivity, whereas disruption of individual KLF4 binding sites within pluripotent-stem-cell-specific enhancers was sufficient to impair enhancer-promoter contacts and reduce the expression of associated genes. Our study provides an integrative view of the complex activities of a lineage-specifying transcription factor and offers novel insights into the nature of the molecular events that follow transcription factor binding.
Identifiants
pubmed: 31548608
doi: 10.1038/s41556-019-0390-6
pii: 10.1038/s41556-019-0390-6
pmc: PMC7339746
mid: NIHMS1057981
doi:
Substances chimiques
KLF4 protein, human
0
Klf4 protein, mouse
0
Kruppel-Like Factor 4
0
Kruppel-Like Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1179-1190Subventions
Organisme : NCI NIH HHS
ID : P01 CA229086
Pays : United States
Organisme : NIDA NIH HHS
ID : DP2 DA043813
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA203702
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007739
Pays : United States
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