Histone O-GlcNAcylation and Potential Biological Functions

Hirosawa, Mitsuko; Hayakawa, Koji; Shiota, Kunio; Tanaka, Satoshi

doi:10.21926/obm.genet.1803036

Cited by 3 publications

(3 citation statements)

References 89 publications

(130 reference statements)

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“…These findings are consistent with the effect and direction of the genetic interactions we observed between OGT and PRC2.1 and OGT and ERK, the direction of ‘information flow’ within the cell ( Figure 7E ), and the effects of our genetic manipulations. OGT could also affect chromatin accessibility by GlcNAcylating histones, although the function and effects of these histone modifications are still poorly understood (Gambetta and Müller, 2015; Hirosawa et al, 2018 ; Konzman et al, 2020 ; Olivier-Van Stichelen et al, 2017 ). Another outstanding question is how OGT is targeted to chromatin and whether this recruitment is dynamic and related to nutrient availability.…”

Section: Discussionmentioning

confidence: 99%

Nutrigenomic regulation of sensory plasticity

Sung

Vaziri

Wilinski

et al. 2023

eLife

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Diet profoundly influences brain physiology, but how metabolic information is transmuted into neural activity and behavior changes remains elusive. Here, we show that the metabolic enzyme O-GlcNAc Transferase (OGT) moonlights on the chromatin of the D. melanogaster gustatory neurons to instruct changes in chromatin accessibility and transcription that underlie sensory adaptations to a high-sugar diet. OGT works synergistically with the Mitogen Activated Kinase/Extracellular signal Regulated Kinase (MAPK/ERK) rolled and its effector stripe (also known as EGR2 or Krox20) to integrate activity information. OGT also cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to decrease chromatin accessibility and repress transcription in the high-sugar diet. This integration of nutritional and activity information changes the taste neurons’ responses to sugar and the flies’ ability to sense sweetness. Our findings reveal how nutrigenomic signaling generates neural activity and behavior in response to dietary changes in the sensory neurons.

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Section: Discussionmentioning

confidence: 99%

Nutrigenomic regulation of sensory plasticity

Sung

Vaziri

Wilinski

et al. 2023

eLife

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“…Although we did not measure cell-specific changes in H3K27me3 (which is not technically feasible), our experiments showing that inhibiting the complex’s catalytic activity prevents OGT-mediated taste plasticity, suggest that H3K27me3 is the silencing signal. However, OGT could also affect chromatin accessibility by GlcNAcylating histones, although the function and effects of these histone modifications are still poorly understood 41,70,101,102 . Our data also showed that OGT catalytic activity is required for chromatin accessibility and gene repression, suggesting that OGT may affect PRC2.…”

Section: Discussionmentioning

confidence: 99%

“…6E), and the effects of our genetic manipulations. OGT could also affect chromatin accessibility by GlcNAcylating histones, although the function and effects of these histone modifications are still poorly understood (Gambetta and Müller, 2015; Hirosawa et al, 2018; Konzman et al, 2020; Olivier-Van Stichelen et al, 2017). Another outstanding question is how OGT is targeted to chromatin and whether this recruitment is dynamic and related to nutrient availability.…”

Section: Discussionmentioning

confidence: 99%

Nutrigenomic Regulation of Sensory Plasticity

Vaziri

Wilinski

Freddolino

et al. 2021

Preprint

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Diet composition has a profound influence on brain physiology and behavior, but the mechanisms through which nutrient information is transmuted into neural changes remain elusive. Here we uncover how the metabolic enzyme O-GlcNAc Transferase (OGT) transforms information about the dietary environment into taste adaptations. We show that in the fly D. melanogaster, OGT decorates the chromatin of the sweet taste neurons and provides the nutrient context to drive changes in chromatin accessibility in response to high dietary sugar. Specifically, we found that OGT cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to promote nutrient-sensitive variations in chromatin openness; these chromatin dynamics result in changes in gene expression and taste plasticity that are dependent on the catalytic activity of OGT. Parallel nutrigenomic signatures were also observed in the lingual epithelium of rats exposed to high dietary sugar, suggesting that this conserved metabolic-epigenetic pathway may also underlie diet-dependent taste changes in mammals. Together our findings reveal a novel role for nutriepigenetic signaling in the brain: amplifying nutrient perturbations into robust changes in chromatin accessibility and transcriptional output that shape neural and behavioral plasticity.

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Functions of HP1 proteins in transcriptional regulation

Schoelz

Riddle

2022

Epigenetics & Chromatin

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In eukaryotes, DNA is packaged into chromatin, which presents significant barriers to transcription. Non-histone chromatin proteins such as the Heterochromatin Protein 1 (HP1) proteins are critical regulators of transcription, contributing to gene regulation through a variety of molecular mechanisms. HP1 proteins are highly conserved, and many eukaryotic genomes contain multiple HP1 genes. Given the presence of multiple HP1 family members within a genome, HP1 proteins can have unique as well as shared functions. Here, we review the mechanisms by which HP1 proteins contribute to the regulation of transcription. Focusing on the Drosophila melanogaster HP1 proteins, we examine the role of these proteins in regulating the transcription of genes, transposable elements, and piRNA clusters. In D. melanogaster, as in other species, HP1 proteins can act as transcriptional repressors and activators. The available data reveal that the precise impact of HP1 proteins on gene expression is highly context dependent, on the specific HP1 protein involved, on its protein partners present, and on the specific chromatin context the interaction occurs in. As a group, HP1 proteins utilize a variety of mechanisms to contribute to transcriptional regulation, including both transcriptional (i.e. chromatin-based) and post-transcriptional (i.e. RNA-based) processes. Despite extensive studies of this important protein family, open questions regarding their functions in gene regulation remain, specifically regarding the role of hetero- versus homodimerization and post-translational modifications of HP1 proteins.

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Histone O-GlcNAcylation and Potential Biological Functions

Cited by 3 publications

References 89 publications

Nutrigenomic regulation of sensory plasticity

Nutrigenomic regulation of sensory plasticity

Nutrigenomic Regulation of Sensory Plasticity

Functions of HP1 proteins in transcriptional regulation

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