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

• DOI: 10.1126/science.aau0583
• Publication Date: 2019-01-04T00:09:11Z
• Authors: Dario Nicetto; Greg Donahue; Tanya Jain; Tao Peng; Simone Sidoli; Lihong Sheng; Thomas Montavon; Justin S. Becker; Jessica M. Grindheim; Kimberly Blahnik; Benjamin A. Garcia; Kai Tan; Roberto Bonasio; Thomas Jenuwein; Kenneth S. Zaret
• Keywords: Heterochromatin protein 1; PRC2

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