HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia
| العنوان: | HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia |
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| المؤلفون: | John J. Cole, Orchi Anannya, Owen J. Sansom, Karen Blyth, Dina Dikovskaya, Maria Grazia Vizioli, Ayala King, Nicholas A. Morrice, Andre Ivanov, Nikolay A. Pchelintsev, Claire Brock, Colin Nixon, Taranjit Singh Rai, William J. Faller, Mark E. Drotar, William Clark, John van Tuyn, David M. Nelson, Tony McBryan, Indrani Manoharan, Rachael N. Hewitt, Peter D. Adams, Kurt I. Anderson |
| المصدر: | Genes & Development. 28:2712-2725 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Genetic Markers, Male, Senescence, Skin Neoplasms, Antineoplastic Agents, Hormonal, Carcinogenesis, Cell Cycle Proteins, Biology, medicine.disease_cause, Cell Line, Histones, Histone H4, Mice, Genetics, medicine, Animals, Humans, Histone Chaperones, Transcription factor, Cellular Senescence, Cell Proliferation, Regulation of gene expression, Papilloma, Molecular biology, Chromatin, Tamoxifen, Histone, Gene Expression Regulation, biology.protein, Female, Cell aging, Transcription Factors, Research Paper, Developmental Biology |
| الوصف: | Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression. |
| وصف الملف: | application/pdf |
| تدمد: | 1549-5477 0890-9369 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d81dc29af8ad7549001dd60339721532Test https://doi.org/10.1101/gad.247528.114Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d81dc29af8ad7549001dd60339721532 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15495477 08909369 |
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