Intragenic CpG islands play important roles in bivalent chromatin assembly of developmental genes.
Sun-Min LeeJungwoo LeeKyung-Min NohWon-Young ChoiSejin JeonGoo Taeg OhJeongsil Kim-HaYoonhee JinSeung-Woo ChoYoung-Joon KimPublished in: Proceedings of the National Academy of Sciences of the United States of America (2017)
CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control. In this paper, we investigated the epigenetic status of iCGIs and found that they too reside in bivalent chromatin in ESCs. Cell type-specific DNA methylation of iCGIs in differentiated cells was linked to the loss of both the H3K4me3 and H3K27me3 marks, and disruption of physical interaction with promoter regions, resulting in transcriptional activation of key regulators of differentiation such as PAXs, HOXs, and WNTs. The differential epigenetic modification of iCGIs appears to be mediated by cell type-specific transcription factors distinct from those bound by promoter, and these transcription factors may be involved in the hypermethylation of iCGIs upon cell differentiation. iCGIs thus play a key role in the cell type-specific regulation of transcription.
Keyphrases
- dna methylation
- genome wide
- transcription factor
- gene expression
- genome wide identification
- copy number
- dna binding
- embryonic stem cells
- single cell
- mental health
- dna damage
- physical activity
- cell therapy
- mass spectrometry
- mesenchymal stem cells
- cell cycle arrest
- oxidative stress
- genome wide analysis
- bioinformatics analysis