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NANOG prion-like assembly mediates DNA bridging

ABSTRACT: NANOG prion-like assembly mediates DNA bridging

PROVIDER: PRJNA787568 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17182334_1.fastq.gz	Fastqsanger.gz
	SRR17182334_2.fastq.gz	Fastqsanger.gz
	SRR17182335_1.fastq.gz	Fastqsanger.gz
	SRR17182335_2.fastq.gz	Fastqsanger.gz
	SRR17182336_1.fastq.gz	Fastqsanger.gz

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NANOG prion-like assembly mediates DNA bridging

Project description:NANOG is a key stem cell pluripotency factor. NANOG’s unique ability to form prion-like assemblies provides a cooperative and concerted DNA bridging mechanism essential for chromatin reorganization and dose-sensitive activation of ground state pluripotency. We take advantage of Hi-C and ChIP-seq experiments to directly address whether NANOG can bridge DNA elements together in human cells, and our results support this.

2022-02-15 | GSE190567 | GEO

NANOG prion-like assembly mediates DNA bridging to facilitate chromatin reorganization and activation of pluripotency.

Project description:Human NANOG expression resets stem cells to ground-state pluripotency. Here we identify the unique features of human NANOG that relate to its dose-sensitive function as a master transcription factor. NANOG is largely disordered, with a C-terminal prion-like domain that phase-transitions to gel-like condensates. Full-length NANOG readily forms higher-order oligomers at low nanomolar concentrations, orders of magnitude lower than typical amyloids. Using single-molecule Förster resonance energy transfer and fluorescence cross-correlation techniques, we show that NANOG oligomerization is essential for bridging DNA elements in vitro. Using chromatin immunoprecipitation sequencing and Hi-C 3.0 in cells, we validate that NANOG prion-like domain assembly is essential for specific DNA recognition and distant chromatin interactions. Our results provide a physical basis for the indispensable role of NANOG in shaping the pluripotent genome. NANOG's unique ability to form prion-like assemblies could provide a cooperative and concerted DNA bridging mechanism that is essential for chromatin reorganization and dose-sensitive activation of ground-state pluripotency.

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