@article{010ebf63b0d9495c88b1b3fb1997da2b,
title = "H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification",
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.",
author = "Dario Nicetto and Greg Donahue and Tanya Jain and Tao Peng and Simone Sidoli and Lihong Sheng and Thomas Montavon and Becker, {Justin S.} and Grindheim, {Jessica M.} and Kimberly Blahnik and Garcia, {Benjamin A.} and Kai Tan and Roberto Bonasio and Thomas Jenuwein and Zaret, {Kenneth S.}",
note = "Funding Information: We thank K. Kaeding and R. McCarthy for comments on the manuscript; Y. Shinkai (RIKEN) for the Setdb1 floxed/floxed strain; the Molecular Pathology and Imaging Core at The University of Pennsylvania (UPenn); T. D. Raabe, J. Henao-Mejia, and J. Richa and the Transgenic and Chimeric Mouse Core (NIH/NIDDK Digestive Diseases Research Center; NIH-P30-DK050306); and the Flow Cytometry and Cell Sorting Facility and the Electron Microscopy Biomedical Research Core Facilities at UPenn. Funding: DFG grant NI-1536 to D.N.; NIH grant GM036477 to K.S.Z.; NIH grant GM110174 to B.A.G; NIH grant DP2MH107055 and the Charles E. Kaufman Foundation (KA2016-85223) to R.B. Publisher Copyright: 2017 {\textcopyright} The Authors, some rights reserved.",
year = "2019",
month = jan,
day = "18",
doi = "10.1126/science.aau0583",
language = "English (US)",
volume = "363",
pages = "294--297",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6424",
}