Frankel Stewart, Rogina Blanka
Department of Pediatrics and Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Aging Cell. 2005 Feb;4(1):53-6. doi: 10.1111/j.1474-9726.2005.00143.x.
Two highly conserved histone deacetylases, Sir2 and Rpd3, have been linked to caloric restriction and the extension of longevity. Because the Drosophila forms of each protein can silence genes in either euchromatin or heterochromatin, we determined whether longevity extension is mediated by silencing in the latter domain. When silencing was increased and decreased using mutations that affect heterochromatin protein 1 (HP1), but have no direct effect upon Sir2 or Rpd3, lifespan was unaffected. Heterochromatin-mediated gene silencing was then modulated without directly influencing HP1 as well as the deacetylases, again yielding no effect on lifespan. Mortality rates were unchanged by all manipulations, indicating that euchromatic targets are likely to be the effectors of deacetylase-mediated longevity extension in Drosophila [corrected]
两种高度保守的组蛋白脱乙酰酶,Sir2和Rpd3,已被证明与热量限制和寿命延长有关。由于果蝇体内这两种蛋白质的形式都能使常染色质或异染色质中的基因沉默,我们决定研究寿命延长是否是由后者区域的基因沉默介导的。当使用影响异染色质蛋白1(HP1)但对Sir2或Rpd3无直接影响的突变来增加或减少基因沉默时,果蝇寿命不受影响。然后在不直接影响HP1以及脱乙酰酶的情况下调节异染色质介导的基因沉默,同样对寿命没有影响。所有操作均未改变死亡率,这表明常染色质靶点可能是果蝇中脱乙酰酶介导的寿命延长的效应器[已修正]