H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes

Establishing and maintaining cell identity depends on the proper regulation of gene expression, as specified by transcription factors and reinforced by epigenetic mechanisms. Among the epigenetic mechanisms, heterochromatin formation is crucial for the preservation of genome stability and the cell type-specific silencing of genes. The heterochromatin-associated histone mark H3K9me3, although traditionally associated with the noncoding portions of the genome, has emerged as a key player in repressing lineage-inappropriate genes and shielding them from activation by transcription factors. Here we describe the role of H3K9me3 heterochromatin in impeding the reprogramming of cell identity and the mechanisms by which H3K9me3 is reorganized during development and cell fate determination.

TrendsH3K9me3, a histone modification associated with heterochromatin, contributes to gene regulation by forming large repressive domains on the chromosomes that can be dynamic in mammalian development.H3K9me3 domains in chromatin prevent binding by diverse transcription factors and constitute a major barrier to reprogram cell identity either by transcription factor overexpression or by somatic cell nuclear transfer.H3K9me3 deposition provides a restriction on developmental potency in the early embryo and promotes the stability of specific differentiated cell fates.Transcription factors and noncoding RNAs have been found to recruit H3K9me3 to particular genomic locations, but a thorough accounting of the mechanisms of tissue-specific variation in H3K9me3 domains is lacking.