| First Author | Nicetto D | Year | 2019 |
| Journal | Science | Volume | 363 |
| Issue | 6424 | Pages | 294-297 |
| PubMed ID | 30606806 | Mgi Jnum | J:271652 |
| Mgi Id | MGI:6280575 | Doi | 10.1126/science.aau0583 |
| Citation | Nicetto D, et al. (2019) H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification. Science 363(6424):294-297 |
| abstractText | 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. |
