Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction.
Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction.
复制标题
DOI：
10.1016/j.molcel.2015.06.027
复制
发表时间：
2015-08-20
期刊：
影响因子：
16
通讯作者：
Morimoto RI
中科院分区：
文献类型：
--
作者：
Labbadia J;Morimoto RI
热休克反应（HSR）对蛋白质稳态和细胞健康至关重要。在后生动物中，衰老与质量控制下降有关，从而增加了蛋白质构象疾病的风险。在这里，我们证明了在C。在线虫中，HSR在成年早期的4小时内急剧下降，与生殖成熟的开始一致。HSR的抑制是由于胁迫基因位点处H3 K27 me 3标记的增加而发生的，其时间由H3 K27脱甲基酶jmjd-3.1的表达减少决定。这导致抑制的染色质状态，其干扰HSF-1结合并抑制响应于应激的转录起始。生殖系干细胞的去除保留了jmjd-3.1的表达，抑制了H3 K27 me 3在应激基因位点的积累，并维持了HSR。这些发现表明，当动物开始繁殖时，生殖细胞系和索马的竞争需求决定了生物体的应激抗性。
The heat shock response (HSR) is essential for proteostasis and cellular health. In metazoans, aging is associated with a decline in quality control, thus increasing the risk for protein conformational disease. Here, we show that in C. elegans, the HSR declines precipitously over a four hour period in early adulthood coincident with the onset of reproductive maturity. Repression of the HSR occurs due to an increase in H3K27me3 marks at stress gene loci, the timing of which is determined by reduced expression of the H3K27 demethylase jmjd-3.1. This results in a repressed chromatin state that interferes with HSF-1 binding and suppresses transcription initiation in response to stress. The removal of germ line stem cells preserves jmjd-3.1 expression, suppresses the accumulation of H3K27me3 at stress gene loci and maintains the HSR. These findings suggest that competing requirements of the germ line and soma dictate organismal stress resistance as animals begin reproduction.