scholarly journals Transcriptional Regulation of ROS Homeostasis by the ERR Subfamily of Nuclear Receptors

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 437
Author(s):  
Charlotte Scholtes ◽  
Vincent Giguère

Reactive oxygen species (ROS) such as superoxide anion (O2•−) and hydrogen peroxide (H2O2) are generated endogenously by processes such as mitochondrial oxidative phosphorylation, or they may arise from exogenous sources like bacterial invasion. ROS can be beneficial (oxidative eustress) as signaling molecules but also harmful (oxidative distress) to cells when ROS levels become unregulated in response to physiological, pathological or pharmacological insults. Indeed, abnormal ROS levels have been shown to contribute to the etiology of a wide variety of diseases. Transcriptional control of metabolic genes is a crucial mechanism to coordinate ROS homeostasis. Therefore, a better understanding of how ROS metabolism is regulated by specific transcription factors can contribute to uncovering new therapeutic strategies. A large body of work has positioned the estrogen-related receptors (ERRs), transcription factors belonging to the nuclear receptor superfamily, as not only master regulators of cellular energy metabolism but, most recently, of ROS metabolism. Herein, we will review the role played by the ERRs as transcriptional regulators of ROS generation and antioxidant mechanisms and also as ROS sensors. We will assess how the control of ROS homeostasis by the ERRs can be linked to physiology and disease and the possible contribution of manipulating ERR activity in redox medicine.

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 933-941 ◽  
Author(s):  
Mary Lou Dula ◽  
Scott G Holmes

Abstract Transcriptional silencing at the HM loci and telomeres in yeast depends on several trans-acting factors, including Rap1p and the Sir proteins. The SUM1-1 mutation was identified by its ability to restore silencing to strains deficient in one or more of these trans-acting factors. The mechanism by which SUM1-1 bypasses the requirement for silencing proteins is not known. We identified four loci that when reduced in dosage in diploid strains increase the ability of SUM1-1 strains to suppress silencing defects. Two of the genes responsible for this effect were found to be MGA2 and SPT23. Mga2p and Spt23p were previously identified as functionally related transcription factors that influence chromatin structure. We find that deletion of MGA2 or SPT23 also increases the efficiency of silencing in haploid SUM1-1 strains. These results suggest that Mga2p and Spt23p are antagonists of silencing. Consistent with this proposal we find that deletion of MGA2 or SPT23 also suppresses the silencing defects caused by deletion of the SIR1 gene or by mutations in the HMR silencer sequences. However, we find that Mga2p and Spt23p can positively affect silencing in other contexts; deletion of either MGA2 or SPT23 decreases mating in strains bearing mutations in the HML-E silencer. Mga2p and Spt23p appear to be a novel class of factors that influence disparate pathways of transcriptional control by chromatin.


Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.


2018 ◽  
Vol 19 (10) ◽  
pp. 3284 ◽  
Author(s):  
Brijesh Kumar Singh ◽  
Rohit Anthony Sinha ◽  
Paul Michael Yen

The thyroid hormone plays a key role in energy and nutrient metabolisms in many tissues and regulates the transcription of key genes in metabolic pathways. It has long been believed that thyroid hormones (THs) exerted their effects primarily by binding to nuclear TH receptors (THRs) that are associated with conserved thyroid hormone response elements (TREs) located on the promoters of target genes. However, recent transcriptome and ChIP-Seq studies have challenged this conventional view as discordance was observed between TH-responsive genes and THR binding to DNA. While THR association with other transcription factors bound to DNA, TH activation of THRs to mediate effects that do not involve DNA-binding, or TH binding to proteins other than THRs have been invoked as potential mechanisms to explain this discrepancy, it appears that additional novel mechanisms may enable TH to regulate the mRNA expression. These include activation of transcription factors by SIRT1 via metabolic actions by TH, the post-translational modification of THR, the THR co-regulation of transcription with other nuclear receptors and transcription factors, and the microRNA (miR) control of RNA transcript expression to encode proteins involved in the cellular metabolism. Together, these novel mechanisms enlarge and diversify the panoply of metabolic genes that can be regulated by TH.


2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Dandan Lu ◽  
Ting Wang ◽  
Staffan Persson ◽  
Bernd Mueller-Roeber ◽  
Jos H.M. Schippers

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jungnam Cho ◽  
Jerzy Paszkowski

It is well documented that transposable elements (TEs) can regulate the expression of neighbouring genes. However, their ability to act in trans and influence ectopic loci has been reported rarely. We searched in rice transcriptomes for tissue-specific expression of TEs and found them to be regulated developmentally. They often shared sequence homology with co-expressed genes and contained potential microRNA-binding sites, which suggested possible contributions to gene regulation. In fact, we have identified a retrotransposon that is highly transcribed in roots and whose spliced transcript constitutes a target mimic for miR171. miR171 destabilizes mRNAs encoding the root-specific family of SCARECROW-Like transcription factors. We demonstrate that retrotransposon-derived transcripts act as decoys for miR171, triggering its degradation and thus results in the root-specific accumulation of SCARECROW-Like mRNAs. Such transposon-mediated post-transcriptional control of miR171 levels is conserved in diverse rice species.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jonathan Fillatre ◽  
Jean-Daniel Fauny ◽  
Jasmine Alexandra Fels ◽  
Cheng Li ◽  
Mary Goll ◽  
...  

In many vertebrates, establishment of Left-Right (LR) asymmetry results from the activity of a ciliated organ functioning as the LR Organizer (LRO). While regulation of the formation of this structure by major signaling pathways has been described, the transcriptional control of LRO formation is poorly understood. Using the zebrafish model, we show that the transcription factors and cofactors mediating or regulating the transcriptional outcome of the Hippo signaling pathway play a pivotal role in controlling the expression of genes essential to the formation of the LRO including ligands and receptors of signaling pathways involved in this process and most genes required for motile ciliogenesis. Moreover, the transcription cofactor, Vgll4l regulates epigenetic programming in LRO progenitors by controlling the expression of writers and readers of DNA methylation marks. Altogether, our study uncovers a novel and essential role for the transcriptional effectors and regulators of the Hippo pathway in establishing LR asymmetry.


2016 ◽  
Vol 10s1 ◽  
pp. JEN.S39887 ◽  
Author(s):  
Thiago Fernando Beckhauser ◽  
José Francis-Oliveira ◽  
Roberto De Pasquale

In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated.


2019 ◽  
Vol 33 (15-16) ◽  
pp. 1069-1082 ◽  
Author(s):  
Navroop K. Dhaliwal ◽  
Luis E. Abatti ◽  
Jennifer A. Mitchell

2008 ◽  
Vol 28 (19) ◽  
pp. 6078-6093 ◽  
Author(s):  
Anke Hoffmann ◽  
Dietmar Spengler

ABSTRACT The generally accepted paradigm of transcription by regulated recruitment defines sequence-specific transcription factors and coactivators as separate categories that are distinguished by their abilities to bind DNA autonomously. The C2H2 zinc finger protein Zac1, with an established role in canonical DNA binding, also acts as a coactivator. Commensurate with this function, p73, which is related to p53, is here shown to recruit Zac1, together with the coactivators p300 and PCAF, to the p21Cip1 promoter during the differentiation of embryonic stem cells into neurons. In the absence of autonomous DNA binding, Zac1's zinc fingers stabilize the association of PCAF with p300, suggesting its scaffolding function. Furthermore, Zac1 regulates the affinities of PCAF substrates as well as the catalytic activities of PCAF to induce a selective switch in favor of histone H4 acetylation and thereby the efficient transcription of p21Cip1. These results are consistent with an authentic coactivator function of Zac1's C2H2 zinc finger DNA-binding domain and suggest coactivation by sequence-specific transcription factors as a new facet of transcriptional control.


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