ATF3 drives senescence by reconstructing accessible chromatin profiles.
ATF3 drives senescence by reconstructing accessible chromatin profiles.
复制标题
ATF3 通过重建可接近的染色质谱来驱动衰老
作者：
Zhang C;Zhang X;Huang L;Guan Y;Huang X;Tian XL;Zhang L;Tao W
染色质结构和基因表达谱在衰老过程中经历了巨大的重建。然而，染色质重构和衰老过程中基因表达之间的调控机制仍然不清楚。染色质可及性是揭示潜在调控元件的一个很好的视角。因此，我们描绘了人脐静脉内皮细胞衰老过程中染色质可及性和基因表达的图景。我们发现，在衰老过程中，染色质可及性发生了重新分配。衰老相关的可及性增强区(IARs)和可及性降低区(DAR)主要分布在远端基因间隔区。DAR与衰老引起的功能衰退相关，而IARs则参与衰老程序的调节。此外，在衰老细胞中，异染色质贡献了IARs的大部分。我们发现AP-1转录因子，尤其是ATF3负责驱动IARs染色质可及性重构。特别是，DNA甲基化与衰老过程中染色质的可及性呈负相关。低DNA甲基化的AP-1基序可能会提高其在IARs中的结合亲和力，并进一步打开附近的染色质。我们的结果描述了染色质可及性的动态景观，其重塑有助于衰老计划。我们还发现了一种细胞衰老调节因子AP-1，它通过组织IARs中的可及性特征来促进衰老。
Chromatin architecture and gene expression profile undergo tremendous reestablishment during senescence. However, the regulatory mechanism between chromatin reconstruction and gene expression in senescence remain elusive. The chromatin accessibility is an excellent perspective to reveal the latent regulatory elements. Thus, we depicted the landscapes of chromatin accessibility and gene expression during HUVECs senescence. We found that chromatin accessibilities are re-distributed during senescence. The senescence related increased accessible regions (IARs) and the decreased accessible regions (DARs) are mainly distributed in distal intergenic regions. The DARs are correlated with the function declines caused by senescence, whereas the IARs are involved in the regulation for senescence program. Moreover, the heterochromatin contributes most of IARs in senescent cells. We identified that the AP-1 transcription factors, especially ATF3 is responsible for driving chromatin accessibility reconstruction in IARs. In particular, DNA methylation is negatively correlated with chromatin accessibility during senescence. AP-1 motifs with low DNA methylation may improve their binding affinity in IARs and further opens the chromatin nearby. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program. And we identified a cellular senescence regulator, AP-1, which promotes senescence through organizing the accessibility profile in IARs.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
16
作者：
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Narita, Masashi
影响因子：
3.7
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Campisi J
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3.3
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Freund A;Laberge RM;Demaria M;Campisi J
通讯作者：
Campisi J
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS