HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci
| Autor: | F. Brad Johnson, Osamu Iwasaki, Andrew V. Kossenkov, Linh Le, Gretchen M. Alicea, Hideki Tanizawa, Ting-Lin B. Yang, Nail Fatkhutdinov, Benjamin G. Bitler, Ken-ichi Noma, Katherine M. Aird, Rugang Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Senescence Heterochromatin HMGB2 Cell Line 03 medical and health sciences Report Gene expression HMGB2 Protein Humans Gene silencing Gene Cellular Senescence Research Articles Genetics Regulation of gene expression Secretory Pathway biology fungi Cell Cycle Checkpoints Cell Biology Chromatin Phenotype 030104 developmental biology Gene Expression Regulation Genetic Loci biology.protein Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201608026 |
| Popis: | In senescence, specific genes encoding secreted factors are excluded from senescence-associated heterochromatin foci, but the mechanisms underlying this senescence-associated secretory phenotype (SASP) are unclear. Aird et al. show that the chromatin-bound protein HMGB2 orchestrates the SASP by preventing heterochromatin spreading to these specific loci. Cellular senescence is a stable cell growth arrest that is characterized by the silencing of proliferation-promoting genes through compaction of chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased transcription of certain genes encoding for secreted factors such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear. In this study, we report that high mobility group box 2 (HMGB2) orchestrates the chromatin landscape of SASP gene loci. HMGB2 preferentially localizes to SASP gene loci during senescence. Loss of HMGB2 during senescence blunts SASP gene expression by allowing for spreading of repressive heterochromatin into SASP gene loci. This correlates with incorporation of SASP gene loci into SAHF. Our results establish HMGB2 as a novel master regulator that orchestrates SASP through prevention of heterochromatin spreading to allow for exclusion of SASP gene loci from a global heterochromatin environment during senescence. |
| Databáze: | OpenAIRE |
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