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

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

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)294-297
Number of pages4
JournalScience
Volume363
Issue number6424
DOIs
StatePublished - Jan 18 2019

ASJC Scopus subject areas

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    Nicetto, D., Donahue, G., Jain, T., Peng, T., Sidoli, S., Sheng, L., Montavon, T., Becker, J. S., Grindheim, J. M., Blahnik, K., Garcia, B. A., Tan, K., Bonasio, R., Jenuwein, T., & Zaret, K. S. (2019). H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification. Science, 363(6424), 294-297. https://doi.org/10.1126/science.aau0583