Bivalent Histone Modifications and Development

Curr Stem Cell Res Ther. 2018;13(2):83-90. doi: 10.2174/1574888X12666170123144743.


Background: Development is an epigenetic regulation dependent event. As one pretranscriptional regulator, bivalent histone modifications were observed to be involved in development recently. It is believed that histone methylation potentially takes charge of cell fate determination and differentiation. The synchronous existence of functionally opposite histone marks at transcript start sequence (TSS) is defined as "Bivalency", which mainly mark development related genes. H3K4me3 and H3K27me3, the prominent histone methylations of bivalency, are implicated in transcriptional activation and transcriptional repression respectively. The delicate balance between H3K4me3 and H3K27me3 produces diverse chromatin architectures, resulting in different transcription states of downstream genes: "poised", "activated" or "repressed".

Objective: In order to explore the developmental role of bivalent histone modification and the underlying mechanism, we did systematic review and rigorous assessment about relative literatures.

Result: Bivalent histone modifications are considered to set up genes for activation during lineage commitment by H3K4me3 and repress lineage control genes to maintain pluripotency by H3K27me3. Summarily, bivalency in stem cells keeps stemness via poising differentiation relevant genes. After receiving developmental signals, the balance between "gene activation" and "gene repression" is broken, which turns genes transcription state from "poised" effect to switch on or switch off effect, thus initiates irreversible and spontaneous differentiation procedures.

Conclusion: Bivalent histone modifications and the associated histone-modifying complexes safeguard proper and robust differentiation of stem cells, thus playing an essential role in development.

Keywords: ESCs differentiation; H3K27me3; H3K4me3; bivalent mark; development; organogenesis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Chromatin / metabolism*
  • Embryonic Stem Cells / cytology
  • Epigenesis, Genetic / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Histones / metabolism*
  • Humans


  • Chromatin
  • Histones