Publication Date
9-22-2021
Journal
Nature Communications
DOI
10.1038/s41467-021-25761-7
PMID
34552088
PMCID
PMC8458463
PubMedCentral® Posted Date
9-22-2021
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Base Sequence, Cell Line, Cell Nucleus, Cellular Reprogramming, Chromatin, DNA, DNA Methylation, Humans, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors, Models, Molecular, Mutation, Nanog Homeobox Protein, Octamer Transcription Factor-3, Promoter Regions, Genetic, Protein Interaction Domains and Motifs, SOXB1 Transcription Factors, Zinc Fingers, Transcription factors, Transcription factors, Transcription, Reprogramming
Abstract
Expression of a few master transcription factors can reprogram the epigenetic landscape and three-dimensional chromatin topology of differentiated cells and achieve pluripotency. During reprogramming, thousands of long-range chromatin contacts are altered, and changes in promoter association with enhancers dramatically influence transcription. Molecular participants at these sites have been identified, but how this re-organization might be orchestrated is not known. Biomolecular condensation is implicated in subcellular organization, including the recruitment of RNA polymerase in transcriptional activation. Here, we show that reprogramming factor KLF4 undergoes biomolecular condensation even in the absence of its intrinsically disordered region. Liquid-liquid condensation of the isolated KLF4 DNA binding domain with a DNA fragment from the NANOG proximal promoter is enhanced by CpG methylation of a KLF4 cognate binding site. We propose KLF4-mediated condensation as one mechanism for selectively organizing and re-organizing the genome based on the local sequence and epigenetic state.
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Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Specialties Commons
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