An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.
An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.
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DOI：
10.1016/j.cell.2008.05.044
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发表时间：
2008-07-25
期刊：
影响因子：
64.5
通讯作者：
Kim SK
中科院分区：
文献类型：
--
作者：
Budovskaya YV;Wu K;Southworth LK;Jiang M;Tedesco P;Johnson TE;Kim SK
定义C.在分子水平上研究线虫衰老过程的基础上，我们利用DNA微阵列实验鉴定了一组1294个年龄调控基因，发现加塔转录因子ELT-3、ELT-5和ELT-6负责这些基因中大部分的年龄调控。elt-5和elt-6的表达在正常老化过程中增加，并且这两种加塔因子抑制elt-3的表达，这显示了在老年蠕虫中表达的相应减少。ELT-3调节大量在老年时改变表达的下游基因，包括UGT-9、Col-144和SOD-3。elt-5（RNAi）和elt-6（RNAi）蠕虫具有延长的寿命，表明elt-3、elt-5和elt-6在衰老过程中起重要的功能作用。这些结果确定了指导C快速衰老过程的转录回路。elegans，并指出，这一电路是由漂移的发展途径，而不是积累的损害。
To define the C. elegans aging process at the molecular level, we used DNA microarray experiments to identify a set of 1294 age-regulated genes and found that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for age regulation of a large fraction of these genes. Expression of elt-5 and elt-6 increases during normal aging, and both of these GATA factors repress expression of elt-3, which shows a corresponding decrease in expression in old worms. elt-3 regulates a large number of downstream genes that change expression in old age, including ugt-9, col-144, and sod-3. elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that elt-3, elt-5, and elt-6 play an important functional role in the aging process. These results identify a transcriptional circuit that guides the rapid aging process in C. elegans and indicate that this circuit is driven by drift of developmental pathways rather than accumulation of damage.