H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification

Science. 2019 Jan 18;363(6424):294-297. doi: 10.1126/science.aau0583. Epub 2019 Jan 3.


Gene silencing by chromatin compaction is integral to establishing and maintaining cell fates. Trimethylated histone 3 lysine 9 (H3K9me3)-marked heterochromatin is reduced in embryonic stem cells compared to differentiated cells. However, the establishment and dynamics of closed regions of chromatin at protein-coding genes, in embryologic development, remain elusive. We developed an antibody-independent method to isolate and map compacted heterochromatin from low-cell number samples. We discovered high levels of compacted heterochromatin, H3K9me3-decorated, at protein-coding genes in early, uncommitted cells at the germ-layer stage, undergoing profound rearrangements and reduction upon differentiation, concomitant with cell type-specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed a pivotal role for H3K9me3 heterochromatin during lineage commitment at the onset of organogenesis and for lineage fidelity maintenance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage*
  • Embryo, Mammalian
  • Embryonic Stem Cells / cytology*
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Silencing
  • Germ Layers / cytology
  • Hepatocytes / cytology
  • Heterochromatin / genetics*
  • Histones / chemistry*
  • Insulin-Secreting Cells / cytology
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organogenesis


  • Heterochromatin
  • Histones