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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. 

Imaging HP1 reveals rules for H3K9 methylation recognition and binding in living cells. 

Abstract Gene Ontology (GO) has been widely used to annotate functions of genes and gene products. Here, we proposed a new method, TripletGO, to deduce GO terms of protein-coding and non-coding genes, through the integration of four complementary pipelines built on transcript expression profile, genetic sequence alignment, protein sequence alignment, and naïve probability. TripletGO was tested on a large set of 5754 genes from 8 species (human, mouse, Arabidopsis, rat, fly, budding yeast, fission yeast, and nematoda) and 2433 proteins with available expression data from the third Critical Assessment of Protein Function Annotation challenge (CAFA3). Experimental results show that TripletGO achieves function annotation accuracy significantly beyond the current state-of-the-art approaches. Detailed analyses show that the major advantage of TripletGO lies in the coupling of a new triplet network-based profiling method with the feature space mapping technique, which can accurately recognize function patterns from transcript expression profiles. Meanwhile, the combination of multiple complementary models, especially those from transcript expression and protein-level alignments, improves the coverage and accuracy of the final GO annotation results. The standalone package and an online server of TripletGO are freely available at https://zhanggroup.org/TripletGO/. 

Heterochromatin is most often associated with eukaryotic organisms. Yet, bacteria also contain areas with densely protein-occupied chromatin that appear to silence gene expression. One nucleoid-associated silencing factor is the conserved protein Hfq. Although seemingly nonspecific in its DNA binding properties, Hfq is strongly enriched at AT-rich DNA regions, characteristic of prophages and mobile genetic elements. Here, we demonstrate that polyphosphate (polyP), an ancient and highly conserved polyanion, is essential for the site-specific DNA binding properties of Hfq in bacteria. Absence of polyP markedly alters the DNA binding profile of Hfq, causes unsolicited prophage and transposon mobilization, and increases mutagenesis rates and DNA damage–induced cell death. In vitro reconstitution of the system revealed that Hfq and polyP interact with AT-rich DNA sequences and form phase-separated condensates, a process that is mediated by the intrinsically disordered C-terminal extensions of Hfq. We propose that polyP serves as a newly identified driver of heterochromatin formation in bacteria. 

Diets rich in sugar, salt, and fat alter taste perception and food preference, contributing to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here, we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons of Drosophila melanogaster flies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity. 

Abstract Motivation Many protein function databases are built on automated or semi-automated curations and can contain various annotation errors. The correction of such misannotations is critical to improving the accuracy and reliability of the databases. Results We proposed a new approach to detect potentially incorrect Gene Ontology (GO) annotations by comparing the ratio of annotation rates (RAR) for the same GO term across different taxonomic groups, where those with a relatively low RAR usually correspond to incorrect annotations. As an illustration, we applied the approach to 20 commonly-studied species in two recent UniProt-GOA releases and identified 250 potential misannotations in the 2018-11-6 release, where only 25% of them were corrected in the 2019-6-3 release. Importantly, 56% of the misannotations are “Inferred from Biological aspect of Ancestor (IBA)” which is in contradiction with previous observations that attributed misannotations mainly to “Inferred from Sequence or structural Similarity (ISS)”, probably reflecting an error source shift due to the new developments of function annotation databases. The results demonstrated a simple but efficient misannotation detection approach that is useful for large-scale comparative protein function studies. Availability https://zhanglab.ccmb.med.umich.edu/RAR Supplementary information Supplementary data are available at Bioinformatics online.