The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance

Abstract

Epigenetic regulation in starvation is important but not fully understood yet. Here we identified the Rpd3 gene, a Drosophila homolog of histone deacetylase 1, as a critical epigenetic regulator for acquiring starvation stress resistance. Immunostaining analyses of Drosophila fat body revealed that the subcellular localization and levels of Rpd3 dynamically changed responding to starvation stress. In response to starvation stress, the level of Rpd3 rapidly increased, and it accumulated in the nucleolus in what appeared to be foci. These observations suggest that Rpd3 plays a role in regulation of rRNA synthesis in the nucleolus. The RT-qPCR and ChIP-qPCR analyses clarified that Rpd3 binds to the genomic region containing the rRNA promoters and activates rRNA synthesis in response to starvation stress. Polysome analyses revealed that the amount of polysomes was decreased in Rpd3 knockdown flies under starvation stress compared with the control flies. Since the autophagy-related proteins are known to be starvation stress tolerance proteins, we examined autophagy activity, and it was reduced in Rpd3 knockdown flies. Taken together, we conclude that Rpd3 accumulates in the nucleolus in the early stage of starvation, upregulates rRNA synthesis, maintains the polysome amount for translation, and finally increases stress tolerance proteins, such as autophagy-related proteins, to acquire starvation stress resistance.

Genomic insights into mite phylogeny, fitness, development, and reproduction

“…According to the KEGG analysis, the N. cucumeris genome harbours at least 108 genes associated with DNA damage-repair such as base/nucleotide excision repairand mismatch repair (Additional file 1: Table S32). In addition to these functional genes, some signal transduction pathways and epigenetic regulation could also play important roles in stress resistence, such as histone deacetylation [130–132].…”

Emerging Role of the Nucleolar Stress Response in Autophagy

“…ChIP analysis has demonstrated that Rpd3 binds to the rDNA promoter. Rpd3 upregulates rRNA synthesis, whereas a Rpd3 knockdown reduces the number of polysomes during starvation (Nakajima et al, 2016). Also, knockdown flies die faster in response to starvation.…”

Tip60 Phosphorylation at Ser 99 Is Essential for Autophagy Induction in Bombyx mori

“…Similarly, Esa1p, the yeast homolog of mammalian Tip60, catalyzes the hyperacetylation of Atg3, which enhances its interaction with Atg8 and facilitates Atg8 lipidation as well as autophagosome maturation under starvation conditions [ 41 ]. Protein acetylation and deacetylation are suggested in diapause [ 15 ], circadian rhythm [ 28 , 29 ], stress resistance and innate immunity in insects [ 14 , 15 ]. In Drosophila , the Tip60 protein complex promotes germline stem cell daughter differentiation in females [ 42 ], whereas, the regulatory mechanisms of Tip60 homologs in autophagy are not well documented in insects.…”

“…In mammals, sirtuin 1 (SIRT1), histone deacetylase 6 (HDAC6), and HDAC1 deacetylate ATG proteins such as ATG5, ATG7, LC3/Atg8 promote autophagy [ 11 , 12 , 13 ]. Mammalian HDAC homologies such as Rpd3, HDAC1, HDAC3, HDAC6, and SIRT2 are suggested to link with stress resistance in Drosophila melanogaster , development in Sarcophaga bullata , and phase polymorphism in locusts [ 14 , 15 , 16 ]. Moreover, parasitoids are more likely to suppress host immune systems and development by impeding histone acetylation and deacetylation [ 17 ].…”