Genome-wide mapping of H4K20me3 in proliferating and senescent IMR90 cells.. Homo sapiens

Cellular senescence is a stable proliferation arrest and tumor suppressor mechanism. Abundance of histone modification, H4K20me3, has been reported to increase in senescent cells. Generally, H4K20me3 promotes formation of compacted transcriptionally silent constitutive heterochromatin, but its specific role in senescence is unknown. Here, we show that in senescent cells H4K20me3 is enriched at specific families of gene repeats (ZNFs, Olfactory Receptors, Protocadherins), and DNA sequences contained within senescence-associated heterochromatin (senescence-associated heterochromatin (SAHF)). Furthermore, in senescent cells, but not proliferating cells, H4K20me3 is also markedly enriched at bodies of repressed genes, including proliferation-promoting genes. Ectopic expression of SUV420H2, responsible for deposition of H4K20me3, reinforces senescence-associated proliferation arrest, and slows proliferation of transformed cells and tumorigenesis in vivo. These results indicate a dedicated role for H4K20me3 in control of nuclear organization and gene expression in senescent cells and stable senescence-associated proliferation arrest and tumor suppression. Overall design: ChIP-seq of H4K20me3 in proliferating (PD32) and replicative senescent (PD86) IMR90 cells was performed using two different H4K20me3 antibodies. In total, four samples are included in the dataset.

细胞衰老（Cellular senescence）是一种稳定的增殖停滞与肿瘤抑制机制。已有研究证实，组蛋白修饰（histone modification）H4K20me3的丰度在衰老细胞中有所升高。通常情况下，H4K20me3可促进形成紧密且转录沉默的组成型异染色质，但其在衰老过程中的具体作用尚未明确。本研究发现，在衰老细胞中，H4K20me3富集于三类特定的基因重复序列家族：锌指蛋白基因（ZNFs）、嗅觉受体基因（Olfactory Receptors）与原钙粘蛋白基因（Protocadherins），同时也富集于衰老相关异染色质（senescence-associated heterochromatin, SAHF）内的DNA序列。此外，仅在衰老细胞而非增殖细胞中，H4K20me3还会显著富集于包括促增殖基因在内的沉默基因体区域。过表达负责催化H4K20me3沉积的SUV420H2，可强化衰老相关的增殖停滞状态，并减缓转化细胞的体外增殖速率与体内肿瘤发生进程。上述结果表明，H4K20me3在衰老细胞的核组织结构调控、基因表达调控，以及稳定的衰老相关增殖停滞与肿瘤抑制过程中发挥专属功能。整体实验设计：本研究采用两种不同的H4K20me3抗体，对增殖期（PD32）与复制性衰老期（PD86）的IMR90细胞开展H4K20me3的染色质免疫共沉淀测序（ChIP-seq），本数据集共包含4个样本。