Altered Oligodendroglial and Neuroglial Gene Expression in Adult Rat Cerebral White Matter Following Short- and Long-Term Ethanol Exposures and Abbreviated Abstinence

Abstract Objectives To determine the effects feeding for 8 (short-term) and 16 weeks (long-term) soy protein isolate on hepatic CYP gene expression. Methods 7-weeks old rats were randomly assigned to either a casein (CAS) or a soy protein isolate (SPI) diet. They were provided the diets ad libitum for 8 and 16 weeks. Rats were euthanized and livers were stored at − 80°C. RNA was extracted from liver samples, and sequenced to obtain transcriptomic data (RNAseq). Ingenuity Pathway Analysis software (IPA, Qiagen, CA) was used in the analysis of global gene expression data. This analysis includes predictions of activation or inhibition of molecules or upstream regulators and functions based on a generated z-score and p-value of overlap (P = 0.05). Z-scores were consider significant when > 2 (activation) and < −2 (inhibition). Results Comparing short- vs long-term feeding revealed an increase in the number of down-regulated CYP genes from only 3 at 8 weeks of SPI diet to 10 at 16 weeks of same diet (P < 0.05). In contrast, upregulated CYP gene numbers showed a small increase in long-term SPI diet compared to short-term, from 14 genes at 8 weeks to 17 genes at 16 weeks (P < 0.05). In addition, we present a predicted activation of the transcription factor Aryl hydrocarbon receptor (AHR, activation z-score = 2.146, P = 4.20E-11), linked to the subsequent activation or up-regulation of various CYPs genes, indirectly leading to the activation and inhibition of two main metabolic functions under SPI feeding: conversion of lipid (lipid metabolism) –predicted to be activated (z-score = 2.089, P = 2.77E-08), and recruitment of phagocytes (inflammatory response) –predicted to be inhibited (z-score = −2.311, P = 2.10E-05). Conclusions Through global gene expression analysis we showed that gene expression of drug-metabolizing cytochrome P450 genes was modified in genetically obese Zucker rats after being fed a soy-based diet for short- and long-term, and that this change could have an important role in attenuation of liver steatosis. Further research is needed to corroborate these results. Funding Sources This study was supported in part by the College of Medicine's University Medical Group (RH) and the Arkansas Biosciences Institute (WB, RH).

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Variation, Variegation and Heritable Gene Repression in S. cerevisiae

Frontiers in Genetics ◽

10.3389/fgene.2021.630506 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kholoud Shaban ◽

Safia Mahabub Sauty ◽

Krassimir Yankulov

Keyword(s):

Gene Expression ◽

Current Knowledge ◽

Regulatory Circuits ◽

Epigenetic Diversity ◽

Short And Long Term ◽

Unstructured Proteins ◽

Gene Regulatory ◽

Gene Regulatory Circuits ◽

Insight Into

Phenotypic heterogeneity provides growth advantages for a population upon changes of the environment. In S. cerevisiae, such heterogeneity has been observed as “on/off” states in the expression of individual genes in individual cells. These variations can persist for a limited or extended number of mitotic divisions. Such traits are known to be mediated by heritable chromatin structures, by the mitotic transmission of transcription factors involved in gene regulatory circuits or by the cytoplasmic partition of prions or other unstructured proteins. The significance of such epigenetic diversity is obvious, however, we have limited insight into the mechanisms that generate it. In this review, we summarize the current knowledge of epigenetically maintained heterogeneity of gene expression and point out similarities and converging points between different mechanisms. We discuss how the sharing of limiting repression or activation factors can contribute to cell-to-cell variations in gene expression and to the coordination between short- and long- term epigenetic strategies. Finally, we discuss the implications of such variations and strategies in adaptation and aging.

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