H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification.
Dario NicettoGreg DonahueTanya JainTao PengSimone SidoliXiaomei HuThomas MontavonJustin S BeckerJessica M GrindheimKimberly BlahnikBenjamin A GarciaKai TanRoberto BonasioThomas JenuweinKenneth S ZaretPublished in: Science (New York, N.Y.) (2019)
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.
Keyphrases
- single cell
- gene expression
- genome wide
- induced apoptosis
- dna methylation
- cell cycle arrest
- embryonic stem cells
- cell fate
- protein protein
- amino acid
- cell therapy
- genome wide identification
- transcription factor
- bioinformatics analysis
- endoplasmic reticulum stress
- stem cells
- cell death
- small molecule
- signaling pathway
- mesenchymal stem cells
- cell proliferation
- intellectual disability
- gold nanoparticles
- high density