Epigenetic regulation of intestinal stem cell differentiation.
Michael P VerziRamesh A ShivdasaniPublished in: American journal of physiology. Gastrointestinal and liver physiology (2020)
To fulfill the lifelong need to supply diverse epithelial cells, intestinal stem cells (ISCs) rely on executing accurate transcriptional programs. This review addresses the mechanisms that control those programs. Genes that define cell behaviors and identities are regulated principally through thousands of dispersed enhancers, each individually <1 kb long and positioned from a few to hundreds of kilobases away from transcription start sites, upstream or downstream from coding genes or within introns. Wnt, Notch, and other epithelial control signals feed into these cis-regulatory DNA elements, which are also common loci of polymorphisms and mutations that confer disease risk. Cell-specific gene activity requires promoters to interact with the correct combination of signal-responsive enhancers. We review the current state of knowledge in ISCs regarding active enhancers, the nucleosome modifications that may enable appropriate and hinder inappropriate enhancer-promoter contacts, and the roles of lineage-restricted transcription factors.
Keyphrases
- transcription factor
- stem cells
- genome wide identification
- genome wide
- cell therapy
- single cell
- dna binding
- public health
- dna methylation
- healthcare
- cell proliferation
- gene expression
- copy number
- high resolution
- oxidative stress
- cancer therapy
- single molecule
- circulating tumor
- binding protein
- bioinformatics analysis
- nucleic acid