BAZ-2 and SET-6 Modulate Aging via BLMP-1 in C. elegans

KANG Xinlei^1,2, CHANG Siyuan¹, MA Li³, WEI Gang³, CAI Shiqing¹*

(¹Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; ²School of Life Science, Fudan University, Shanghai 200438, China; ³Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China)

Abstract:

This study aims to explore whether two epigenetic regulators, BAZ-2 and SET-6, modulate aging via BLMP-1 by regulating the expression of nuclear genes encoding mitochondrial protein in C. elegans (Caenorhabditis elegans). Through data analysis in JASPAR database, the binding site of the transcription factor BLMP-1 was found to be enriched in the sequence of promoter region of up-regulated expression genes found in both baz-2 and set-6 mutant worms. By knocking out blmp-1 in baz-2 and set-6 mutant worms respectively, blmp-1;baz-2 and blmp-1;set-6 double mutant worms were obtained and their lifespan, pharyngeal pumping, basal and enhanced slowing responses, capacity of oxidative resistance and the expression of nuclear genes encoding mitochondrial proteins were analyzed. The results show that ablation of blmp-1 abolishes the lifespan extension, behavioral preservation and up-regulated expression of nuclear genes encoding mitochondrial proteins in aging baz-2 or set-6 mutant worms. This study suggests that BAZ-2 and SET-6 modulate aging via BLMP-1 in C. elegans.

CSTR: 32200.14.cjcb.2021.07.0018