Regulation of animal behavior by epigenetic regulators.

Epigenetic regulation in animals induces rapid and long-lasting effects on gene expression in response to environmental changes that frequently affect animal behavior. In the last decade, accumulating studies have revealed how epigenetic regulation affects the behavior of animals, such as learning and memory, mating and courtship, the circadian sleep-wake cycle, and foraging/starvation-induced hyperactivity. In each section of this review, we discuss what we have learned from studies with mammals, mostly mouse models.

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

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.

Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes.

Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj).

Epigenetic regulation of starvation-induced autophagy in Drosophila by histone methyltransferase G9a.

Epigenetics is now emerging as a key regulation in response to various stresses. We herein identified the Drosophila histone methyltransferase G9a (dG9a) as a key factor to acquire tolerance to starvation stress. The depletion of dG9a led to high sensitivity to starvation stress in adult flies, while its overexpression induced starvation stress resistance.

Polycomb-dependent nucleolus localization of Jumonji/Jarid2 during spermatogenesis.

Jumonji/Jarid2 (dJmj) has been identified as a component of Polycomb repressive complex 2. However, it is suggested that dJmj has both PRC-dependent and -independent roles. Subcellular localization of dJmj during spermatogenesis is unknown.

The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance.

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.

Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo.

G9a is one of the histone H3 Lys 9 (H3K9) specific methyltransferases first identified in mammals. Drosophila G9a (dG9a) has been reported to induce H3K9 dimethylation in vivo, and the target genes of dG9a were identified during embryonic and larval stages. Although dG9a is important for a variety of developmental processes, the link between dG9a and signaling pathways are not addressed yet.

Genomewide identification of target genes of histone methyltransferase dG9a during Drosophila embryogenesis.

Post-translational modification of the histone plays important roles in epigenetic regulation of various biological processes. Among the identified histone methyltransferases (HMTases), G9a is a histone H3 Lys 9 (H3K9)-specific example active in euchromatic regions. Drosophila G9a (dG9a) has been reported to feature H3K9 dimethylation activity in vivo.

Control of e2f1 and PCNA by Drosophila transcription factor DREF.

DREF (DNA replication-related element-binding factor), a zinc finger type transcription factor required for proper cell cycle progression in both mitotic and endocycling cells, is a positive regulator of E2F1, an important transcription factor which regulates genes related to the S-phase of the cell cycle. DREF and E2F1 regulate similar sets of replication-related genes, including proliferating cell nuclear antigen (PCNA), and play roles in the G1 to S phase transition. However, the relationships between dref and e2f1 or PCNA during development are poorly understood.

Temporal and spatial pattern of dref expression during Drosophila bristle development.

The DNA replication-related element-binding factor (DREF) is a BED finger-type transcription factor that has important roles in cell cycle progression. In an earlier study, we showed that DREF is required for endoreplication during posterior scutellar macrochaete development. However, dynamic change in the dref expression in the cell lineage is unclear.

Dynamics of endoreplication during Drosophila posterior scutellar macrochaete development.

Endoreplication is a variant type of DNA replication, consisting only of alternating G1 and S phases. Many types of Drosophila tissues undergo endoreplication. However, the timing and the extent to which a single endocycling macrochaete undergoes temporally programmed endoreplication during development are unclear.

Effect of αB-crystallin on protein aggregation in Drosophila.

Disorganisation and aggregation of proteins containing expanded polyglutamine (polyQ) repeats, or ectopic expression of α-synuclein, underlie neurodegenerative diseases including Alzheimer's, Parkinson, Huntington, Creutzfeldt diseases. Small heat-shock proteins, such as αB-crystallin, act as chaperones to prevent protein aggregation and play a key role in the prevention of such protein disorganisation diseases. In this study, we have explored the potential for chaperone activity of αB-crystallin to suppress the formation of protein aggregates.

Roles of histone H3K9 methyltransferases during Drosophila spermatogenesis.

Epigenetic regulation of gene expression by covalent modification of histones is important for germ line cell development. In mammals, histone H3 lysine 9 (H3K9)-specific histone methyltransferases (HMTases), such as G9a, SETDB1, and SUV39H, play critical roles, but the contribution of H3K9-specific HMTases in Drosophila remains to be clarified, especially in male sperm. Here, we performed immunocytochemical analyses with a specific antibody to dG9a, Drosophila G9a ortholog, and demonstrated localization in the cytoplasm from the growth to elongation stages of spermatogenesis.