Hepatocyte Nuclear Factor 4-Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver.

Cell-fate determination is influenced by interactions between master transcription factors (TFs) and cis-regulatory elements. Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control onset of hepatocyte cell fate. Using analysis of genome-wide histone modifications, DNA methylation, and hydroxymethylation in mouse hepatocytes, we show that HNF4A occupies active enhancers in hepatocytes and is essential for active histone and DNA signatures, especially acetylation of lysine 27 of histone 3 (H3K27ac) and 5-hydroxymethylcytosine (5hmC). In mice lacking HNF4A protein in hepatocytes, we observed a decrease in both H3K27ac and hydroxymethylation at regions bound by HNF4A. Mechanistically, HNF4A-associated hydroxymethylation (5hmC) requires its interaction with ten-eleven translocation methylcytosine dioxygenase 3 (TET3), a protein responsible for oxidation from 5mC to 5hmC. Furthermore, HNF4A regulates TET3 expression in liver by directly binding to an enhancer region. Conclusion: In conclusion, we identified that HNF4A is required for the active epigenetic state at enhancers that amplifies transcription of genes in hepatocytes.

Physiological and genome-wide RNA-sequencing analyses identify candidate genes in a nitrogen-use efficient potato cv. Kufri Gaurav.

Nitrogen (N) is an important nutrient for plant growth. However, its excess application leads to environmental damage. Hence, improving nitrogen use efficiency (NUE) of plant is one of the plausible options to solve the problems. Aim of this study was to identify candidate genes involved in enhancing NUE in potato cv. Kufri Gaurav (N efficient). Plants were grown in aeroponic with two contrasting N regimes (low N: 0.75 mM, and high N: 7.5 mM). Higher NUE in Kufri Gaurav was observed in low N based on the parameters like NUE, NUpE (N uptake efficiency), NUtE (N utilization efficiency) and AgNUE (agronomic NUE). Further, global gene expression profiles in root, leaf and stolon tissues were analyzed by RNA-sequencing using Ion Proton™ System. Quality data (≥Q20) of 2.04-2.73 Gb per sample were mapped with the potato genome. Statistically significant (P ≤ 0.05) differentially expressed genes (DEGs) were identified such as 176 (up-regulated) and 30 (down-regulated) in leaves, 39 (up-regulated) and 105 (down-regulated) in roots, and 81 (up-regulated) and 694 (down-regulated) in stolons. The gene ontology (GO) terms like metabolic process, cellular process and catalytic activity were predominant. Our RT-qPCR analysis confirmed the gene expression profiles of RNA-seq. Overall, we identified candidate genes associated with improving NUE such as superoxide dismutase, GDSL esterase lipase, probable phosphatase 2C, high affinity nitrate transporters, sugar transporter, proline rich proteins, transcription factors (VQ motif, SPX domain, bHLH) etc. Our findings suggest that these candidate genes probably play crucial roles in enhancing NUE in potato.

Coprevalence of parasitic infections and diabetes in Sub-Himalayan region of Northern India.

OBJECTIVES: Parasitic infections such as toxoplasmosis, hydatidosis, and cysticercosis infect a large population worldwide. Toxoplasma gondii in the pancreas could damage the pancreatic cells. Hence, insulin secretion would be affected which leads to increased risk of diabetes. The present study was designed to investigate the cooccurrence of parasitic infections in patients with diabetes. METHODS: A total of 256 confirmed parasitic serum samples were included in the study, of which 95 were positive for toxoplasmosis, 87 for hydatidosis, and 74 for cysticercosis infection. These samples were then analyzed for hyperglycemia. RESULTS: In case of hydatidosis, the frequency of hyperglycemia was 14.94%, followed by cysticercosis (10.8%) and toxoplasmosis (8.42%). The frequency of insulin resistance was analyzed in these hyperglycemic samples. The coprevalence of diabetes was higher in case of hyperglycemic hydatidosis patient samples (11.49%), followed by cysticercosis (8.10%) while the coprevalence of diabetes was minimum (6.31%) in toxoplasmosis patients samples. Thus, the overall prevalence of diabetes with parasitic infections was 8.6%. CONCLUSION: The study suggested the coexistence of hyperglycemia in hydatidosis, cysticercosis, and toxoplasmosis infected samples. However, higher prevalence of high glucose level was detected among hydatidosis infected samples. Thus, suggested individuals infected with hydatidosis were more susceptible for diabetes in comparison to toxoplasmosis and cysticercosis.