Raw data for Sati et al., 2020

These datasets are contain Beta gal assay images, DAPI stained nuclei and 3D FISH images from oncogene and replicative senescent cells. The Betagal assay was performed to demonstrate the senescent condition. The DAPI stained nuclei images are from different siRNA treated OIS samples. The FISH images display the presence of SHADs in SAHFs.

The Summary of work:
While transcriptional and epigenetic changes associated with senescence are well studied, the role of the extensive senescence-associated 3D genome reorganization remains elusive. Here, we have generated genome wide chromatin interaction maps, epigenetic, replication-timing, whole genome bisulfite sequencing and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene induced senescence (OIS). We identify Senescence Associated Heterochromatin Domains (SAHDs). Differential intra vs inter SAHD interactions lead to the formation of senescence associated heterochromatin foci (SAHFs) in OIS but not in RS. This OIS-specific configuration brings active genes located in genomic regions adjacent to SAHDs in close spatial proximity and favours their expression. Finally, screening of factors for SAHF induction revealed DNMT1 as a novel component that induces SAHFs by promoting HMGA2 expression. Upon DNMT1 depletion, OIS cells transition to a 3D genome conformation akin to that of cells in replicative senescence. These data show how multi-omics and imaging can identify critical features of RS and OIS and discover new determinants of acute senescence and SAHF formation.

本数据集包含取自癌基因诱导衰老细胞与复制性衰老细胞的β半乳糖苷酶染色试验（Beta gal assay）图像、DAPI染色细胞核图像以及三维荧光原位杂交（3D FISH）图像。该β半乳糖苷酶染色试验用于验证细胞的衰老状态。上述DAPI染色细胞核图像取自经不同小干扰RNA（siRNA）处理的癌基因诱导衰老（oncogene induced senescence, OIS）样本。本次三维荧光原位杂交图像展示了衰老相关异染色质焦点（senescence associated heterochromatin foci, SAHFs）内SHADs的存在情况。

研究工作概述：
尽管与衰老相关的转录及表观遗传变化已得到广泛研究，但大规模衰老相关3D基因组重编程的调控作用仍未明确。本研究从进入复制性衰老（replicative senescence, RS）或发生癌基因诱导衰老（OIS）的细胞中，获取了全基因组染色质相互作用图谱、表观遗传组数据、复制时序数据、全基因组亚硫酸氢盐测序数据以及基因表达谱。我们成功鉴定出衰老相关异染色质结构域（Senescence Associated Heterochromatin Domains, SAHDs）。衰老相关异染色质结构域内部与之间的差异化相互作用，使得癌基因诱导衰老样本中形成衰老相关异染色质焦点（SAHFs），而复制性衰老样本中并未出现该现象。这种癌基因诱导衰老特异性的染色质构象，使位于衰老相关异染色质结构域相邻基因组区域的活性基因在空间上紧密靠近，从而促进这些基因的表达。最后，通过对衰老相关异染色质焦点诱导因子的筛选，我们发现DNA甲基转移酶1（DNMT1）是一种新型调控因子，可通过促进高迁移率族蛋白A2（HMGA2）的表达来诱导衰老相关异染色质焦点的形成。当DNA甲基转移酶1被敲低后，癌基因诱导衰老细胞的3D基因组构象会转变为与复制性衰老细胞相似的状态。本研究数据证实了多组学与成像技术如何助力解析复制性衰老与癌基因诱导衰老的关键特征，并发现了急性衰老及衰老相关异染色质焦点形成的新型调控因子。