Histone methyltransferase G9a is a key regulator of the starvation-induced behaviors in Drosophila melanogaster

Abstract

Organisms have developed behavioral strategies to defend themselves from starvation stress. Despite of their importance in nature, the underlying mechanisms have been poorly understood. Here, we show that Drosophila G9a (dG9a), one of the histone H3 Lys 9-specific histone methyltransferases, functions as a key regulator for the starvation-induced behaviors. RNA-sequencing analyses utilizing dG9a null mutant flies revealed that the expression of some genes relating to gustatory perception are regulated by dG9a under starvation conditions. Reverse transcription quantitative-PCR analyses showed that the expression of gustatory receptor genes for sensing sugar are up-regulated in starved dG9a null mutant. Consistent with this, proboscis extension reflex tests indicated that dG9a depletion increased the sensitivity to sucrose under starvation conditions. Furthermore, the locomotion activity was promoted in starved dG9a null mutant. We also found that dG9a depletion down-regulates the expression of insulin-like peptide genes that are required for the suppression of starvation-induced hyperactivity. Furthermore, refeeding of wild type flies after starvation conditions restores the hyperactivity and increased sensitivity to sucrose as well as dG9a expression level. These data suggest that dG9a functions as a key regulator for the decision of behavioral strategies under starvation conditions.

RNA-binding protein Syncrip regulates Starvation-Induced Hyperactivity in adultDrosophila

“…Starvation-Induced Hyperactivity (SIH) has been observed in different species [3][4][5][6][7][8][9][10][11][12], suggesting that it has a genetic component. SIH facilitates food acquisition and energy intake when food is available [7], but it increases energy expenditure and makes starved animals even more vulnerable when food is not available [4].…”

“…Tyramine beta hydroxylase (Tbh) [7], and dG9a [9]. Majority of these candidates play important roles in relaying metabolic information to neurons.…”

“…Recently, dG9a was shown to regulate SIH in adult Drosophila [9]. Gene dG9a encodes a histone methyltransferase, suggesting that SIH is also regulated at the epigenetic level.…”

Epigenetic regulator G9a provides glucose as a sweet key to stress resistance

“…melanogaster G9a in the response to viral infection and starvation. Additional reports demonstrated requirements for G9a in metabolic and hypoxia adaptation in mice and in mammalian cell culture [16–19]. In these studies, G9a influenced survival by regulating the expression of specific stress response pathways, such as signaling through the Janus kinase-Signal Transducer and Activator of Transcription (Jak-STAT) innate immune response pathway, the hypoxia response master regulator hypoxia inducible factor 1 (HIF-1), or the cytoprotective Phosphoinositide 3-kinase/Protein kinase B/Nuclear factor (erythroid-derived 2)-like 2 (PI3K/PKB/Nrf2) axis.…”

“…These findings are interesting because they suggest that G9a is a core component of a mechanism that connects the regulation of specific stress response genes (here oxidative stress response genes) to the control of energy metabolism. This regulatory pathway may be relevant in multiple adverse conditions, because G9a has been implicated in several different stress responses across species ([16–19] and Figure S10 in [15]). The key roles of G9a in mediating these responses may be assuring adequate energy allocation during times of stress as well as mediating a buffered induction of specific stress response gene sets.…”