HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci

被引：144

作者：

Aird, Katherine M. ^{[1
]}

Iwasaki, Osamu ^{[1
]}

Kossenkov, Andrew V. ^{[2
]}

Tanizawa, Hideki ^{[1
]}

Fatkhutdinov, Nail ^{[1
,4
]}

Bitler, Benjamin G. ^{[1
]}

Le, Linh ^{[1
,5
]}

Alicea, Gretchen ^{[3
]}

Yang, Ting-Lin ^{[6
]}

Johnson, Brad ^{[6
]}

Noma, Ken-ichi ^{[1
]}

Zhang, Rugang ^{[1
]}

机构：

[1] Wistar Inst Anat & Biol, Gene Express & Regulat Program, 3601 Spruce St, Philadelphia, PA 19104 USA

[2] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, 3601 Spruce St, Philadelphia, PA 19104 USA

[3] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis Program, 3601 Spruce St, Philadelphia, PA 19104 USA

[4] Kazan Fed Univ, Kazan 42000, Russia

[5] Univ Penn, Cell & Mol Biol Grad Grp, Philadelphia, PA 19014 USA

[6] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19014 USA

来源：

JOURNAL OF CELL BIOLOGY | 2016年 / 215卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ONCOGENE-INDUCED SENESCENCE; CELLULAR SENESCENCE; HUMAN-CELLS; CANCER; HETEROCHROMATIN; PROMOTES; SUPPRESSION; PROTEINS; NETWORK; DISEASE;

D O I：

10.1083/jcb.201608026

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：325 / 334

页数：10

共 35 条

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Chemokine signaling via the CXCR2 receptor reinforces senescence [J].