Genomic Transcriptional Activation Research Articles

Methylome Response to Proteasome Inhibition by Pseudomonas syringae Virulence Factor Syringolin A.

DNA methylation is an important epigenetic mark required for proper gene expression and silencing of transposable elements. DNA methylation patterns can be modified by environmental factors such as pathogen infection, in which modification of DNA methylation can be associated with plant resistance. To counter the plant defense pathways, pathogens produce effector molecules, several of which act as proteasome inhibitors. Here, we investigated the effect of proteasome inhibition by the bacterial virulence factor syringolin A (SylA) on genome-wide DNA methylation. We show that SylA treatment results in an increase of DNA methylation at centromeric and pericentromeric regions of Arabidopsis chromosomes. We identify several CHH differentially methylated regions (DMRs) that are enriched in the proximity of transcriptional start sites. SylA treatment does not result in significant changes in small RNA composition. However, significant changes in genome transcriptional activity can be observed, including a strong upregulation of resistance genes that are located on chromosomal arms. We hypothesize that DNA methylation changes could be linked to the upregulation of some atypical members of the de novo DNA methylation pathway, namely AGO3, AGO9, and DRM1. Our data suggests that modification of genome-wide DNA methylation resulting from an inhibition of the proteasome by bacterial effectors could be part of an epi-genomic arms race against pathogens. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Genomic and non-genomic pathways are both crucial for peak induction of neurite outgrowth by retinoids

Retinoic acid (RA) is the active metabolite of vitamin A and essential for many physiological processes, particularly the induction of cell differentiation. In addition to regulating genomic transcriptional activity via RA receptors (RARs) and retinoid X receptors (RXRs), non-genomic mechanisms of RA have been described, including the regulation of ERK1/2 kinase phosphorylation, but are poorly characterised. In this study, we test the hypothesis that genomic and non-genomic mechanisms of RA are regulated independently with respect to the involvement of ligand-dependent RA receptors. A panel of 28 retinoids (compounds with vitamin A-like activity) showed a marked disparity in genomic (gene expression) versus non-genomic (ERK1/2 phosphorylation) assays. These results demonstrate that the capacity of a compound to activate gene transcription does not necessarily correlate with its ability to regulate a non-genomic activity such as ERK 1/2 phosphorylation. Furthermore, a neurite outgrowth assay indicated that retinoids that could only induce either genomic, or non-genomic activities, were not strong promoters of neurite outgrowth, and that activities with respect to both transcriptional regulation and ERK1/2 phosphorylation produced maximum neurite outgrowth. These results suggest that the development of effective retinoids for clinical use will depend on the selection of compounds which have maximal activity in non-genomic as well as genomic assays.

A Weakened Geomagnetic Field: Effects on Genomic Transcriptiln Activity, Learning, and Memory in Drosophila Melanogaster

Neurodegenerative diseases result from a complex interaction between unfavorable environmental factors and the individual characteristics of the genome which predispose to disease development. Drosophila provides a suitable system for studies of the relationship between genomic organization and chromosomal architecture producing cognitive impairments. We present here the results of complex investigations of the effects of attenuation of the geomagnetic field (by screening) on genomic transcriptional activity, learning ability, and the formation of intermediate-term memory in Drosophila melanogaster. In this stress, a relationship was seen between modifications to transcriptional activity and the structure of the LIMK1 gene – a key enzyme in the actin remodeling cascade. Impairments to intermediate-term memory were seen on exposure to a weak static magnetic field in Canton-S wild-type flies. Conversely, this same stress restored learning ability and memory formation in agnts3 mutants.

Hydroxylated Polybrominated Diphenyl Ethers Exert Estrogenic Effects via Non-Genomic G Protein-Coupled Estrogen Receptor Mediated Pathways.

Background:Numerous studies have indicated the estrogenic effects of polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs (OH-PBDEs). However, the previous mechanistic studies focused on their estrogenic effects through genomic transcriptional activation of estrogen receptors.Objective:The present study aimed to investigate the estrogenic effects of PBDEs and OH-PBDEs via nongenomic G protein–coupled estrogen receptor (GPER) pathways.Methods:The binding affinities of 12 PBDEs and 18 OH-PBDEs with GPER were determined by a fluorescence competitive binding assay in a human breast cancer cell line (SKBR3). Molecular docking was performed to simulate the interactions. Their activities on GPER pathways were investigated by detecting calcium mobilization and cyclic adenosine monophosphate (cAMP) accumulation in SKBR3 cells. The effects on SKBR3 cell migration were investigated using Boyden chamber and wound-healing assays.Results:Our results showed that 11 of the OH-PBDEs but none of the PBDEs bound to GPER directly. Relative binding affinities ranged from 1.3% to 20.0% compared to . Docking results suggested that the hydroxyl group played an essential role in the binding of OH-PBDEs to GPER by forming hydrogen bond interactions. Most of the OH-PBDEs activated subsequent GPER signaling pathways. Among them, 4ʹ-OH-BDE-049, 5ʹ-OH-BDE-099, and 3ʹ-OH-BDE-154 displayed the highest activity with lowest effective concentrations (LOECs) of . These three OH-PBDEs also promoted SKBR3 cell migration via GPER pathways with LOECs of .Conclusion:OH-PBDEs could bind to GPER, activate the subsequent signaling pathways, and promote SKBR3 cell migration via GPER pathways. OH-PBDEs might exert estrogenic effects by a novel nongenomic mechanism involving the activation of GPER at nanomolar concentrations. https://doi.org/10.1289/EHP2387

Genomic transcriptional activity and the structure of chromatin.

Nucleic acid hybridisation has shown that micrococcal nuclease-derived chromatin subunits from the cells of Xenopus laevis contain fragments of ribosomal 28S, 18S and 5S RNAS within the population of 200 base-pair pieces of DNA. Subunits from cultured embryonic cells actively transcribing ribosomal RNA contain only 70-74% of the cistrons present in undigested wild-type DNA, while subunits from adult erythrocytes not active in RNA transcription contain close to 90% of the ribosomal cistrons in native chromatin.