G-quadruplex DNA structures in human stem cells and differentiation.
Katherine G ZynerAngela SimeoneSean M FlynnColm DoyleGiovanni MarsicoSantosh AdhikariGuillem PortellaDavid TannahillSamantha KendrickPublished in: Nature communications (2022)
The establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation.
Keyphrases
- dna methylation
- gene expression
- stem cells
- embryonic stem cells
- endothelial cells
- genome wide
- single cell
- circulating tumor
- cell therapy
- copy number
- single molecule
- induced pluripotent stem cells
- cell free
- high resolution
- cell fate
- induced apoptosis
- electronic health record
- binding protein
- papillary thyroid
- big data
- mass spectrometry
- cell death
- squamous cell
- pi k akt