M33 condenses chromatin through nuclear body formation and methylation of both histone H3 lysine 9 and lysine 27
| Autor: | Ya-Li Yao, Chiung-Chyi Shen, Wen-Ming Yang, Yu-Ru Lin, You-Yu Liu, Hsin-Chi Lan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Polycomb Repressive Complex 1
Chemistry Heterochromatin Lysine fungi Nuclear Proteins Cell Biology Methylation Chromatin Cell biology Histones chemistry.chemical_compound Histone H3 Prophase HEK293 Cells Chromobox Protein Homolog 5 Constitutive heterochromatin Humans Molecular Biology DNA Cells Cultured SUV39H1 |
| Zdroj: | Biochimica et biophysica acta. Molecular cell research. 1868(11) |
| ISSN: | 1879-2596 |
| Popis: | Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases. |
| Databáze: | OpenAIRE |
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