Chromatin Modification in iPS Cells

Scientists experimentally induce chromatin remodeling to enhance the conversion of cells into pluripotent stem cells. Chromatin is composed of nucleosomes—structures consisting of DNA wound around histone proteins.  

Remodeling transforms the condensed chromatin to a relaxed form,  inducing the gene expression necessary for pluripotency.

During remodeling, the histones are modified by specific enzymes, and entire nucleosomes relocate, altering gene expression. 

Methylation strengthens the interaction between histones and DNA, suppressing transcription of genes involved in differentiation. In contrast, histone demethylases remove methyl groups to activate genes involved in pluripotency. 

Unlike methylation, acetylation weakens histones’ interaction with DNA and loosens the chromatin to make it accessible to transcription factors. Histone acetyltransferases and deacetylases catalyze acetylation and deacetylation.    

Histone variants can replace the major histone proteins, leading to chromatin remodeling. For example, when the variant H2AZ is incorporated into the nucleosome it increases the accessibility of DNA to specific transcription factors and promotes the conversion of somatic cells to iPS cells.