HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci.
HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci.
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DOI：
10.1083/jcb.201608026
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发表时间：
2016-11-07
期刊：
影响因子：
--
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Aird KM;Iwasaki O;Kossenkov AV;Tanizawa H;Fatkhutdinov N;Bitler BG;Le L;Alicea G;Yang TL;Johnson FB;Noma KI;Zhang R
在衰老过程中，编码分泌因子的特定基因被排除在衰老相关的异染色质病灶之外，但这种衰老相关分泌表型（SASP）的机制尚不清楚。Aird等人表明，染色质结合蛋白HMGB2通过阻止异染色质扩散到这些特定位点来协调SASP。细胞衰老是一种稳定的细胞生长停滞，其特征在于通过染色体压缩成衰老相关异染色质灶（SAHF）来沉默促增殖基因。特别地，衰老还伴随着编码分泌因子如细胞因子和趋化因子的某些基因的转录增加，称为衰老相关分泌表型（SASP）。SASP基因如何被排除在SAHF介导的全局基因沉默之外尚不清楚。在这项研究中，我们报告，高迁移率族蛋白2（HMGB2）编排染色质景观的SASP基因位点。HMGB2在衰老过程中优先定位于SASP基因位点。衰老过程中HMGB2的缺失通过使抑制性异染色质扩散到SASP基因位点而使SASP基因表达钝化。这与SASP基因位点掺入SAHF相关。我们的研究结果建立了HMGB2作为一种新的主调节器，通过防止异染色质扩散来协调SASP，以允许在衰老过程中从全球异染色质环境中排除SASP基因位点。
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.
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影响因子：
16
作者：
Chandra, Tamir;Kirschner, Kristina;Thuret, Jean-Yves;Pope, Benjamin D.;Ryba, Tyrone;Newman, Scott;Ahmed, Kashif;Samarajiwa, Shamith A.;Salama, Rafik;Carroll, Thomas;Stark, Rory;Janky, Rekin's;Narita, Masako;Xue, Lixiang;Chicas, Agustin;Nunez, Sabrina;Janknecht, Ralf;Hayashi-Takanaka, Yoko;Wilson, Michael D.;Marshall, Aileen;Odom, Duncan T.;Babu, M. Madan;Bazett-Jones, David P.;Tavare, Simon;Edwards, Paul A. W.;Lowe, Scott W.;Kimura, Hiroshi;Gilbert, David M.;Narita, Masashi
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DOI：
10.1158/1541-7786.mcr-10-0398
发表时间：
2010-12
期刊：
Molecular cancer research : MCR
影响因子：
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作者：
Li H;Cai Q;Godwin AK;Zhang R
通讯作者：
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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