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

Nicetto, Dario; Donahue, Greg; Jain, Tanya; Peng, Tao; Sidoli, Simone; Sheng, Lihong; Montavon, Thomas; Becker, Justin S.; Grindheim, Jessica M.; Blahnik, Kimberly; Garcia, Benjamin A.; Tan, Kai; Bonasio, Roberto; Jenuwein, Thomas; Zaret, Kenneth S.

doi:10.1126/science.aau0583

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

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Montavon, Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Jenuwein, Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://science.sciencemag.org/content/363/6424/294.long
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引用

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, 294-297. doi: 10.1126/science.aau0583.

引用: https://hdl.handle.net/21.11116/0000-0003-6E4C-E

要旨

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.