Selenium regulation of gene expression-implications for the selenium requirement and function

Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.

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Differential fates of introns in gene expression due to global alternative splicing

Human Genetics ◽

10.1007/s00439-021-02409-6 ◽

2021 ◽

Author(s):

Anjani Kumari ◽

Saam Sedehizadeh ◽

John David Brook ◽

Piotr Kozlowski ◽

Marzena Wojciechowska

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Neuromuscular Disorders ◽

Regulation Of Gene Expression ◽

Protein Isoforms ◽

Circular Rnas ◽

Surveillance Systems ◽

Myotonic Dystrophy Type 2 ◽

New Vision ◽

And Function

AbstractThe discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology.

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Critical Role of Types 2 and 3 Deiodinases in the Negative Regulation of Gene Expression by T3 in the Mouse Cerebral Cortex

Endocrinology ◽

10.1210/en.2011-1905 ◽

2012 ◽

Vol 153 (6) ◽

pp. 2919-2928 ◽

Cited By ~ 47

Author(s):

Arturo Hernandez ◽

Beatriz Morte ◽

Mónica M. Belinchón ◽

Ainhoa Ceballos ◽

Juan Bernal

Keyword(s):

Gene Expression ◽

Cerebral Cortex ◽

Thyroid Hormone ◽

Critical Role ◽

Regulation Of Gene Expression ◽

Control Of Gene Expression ◽

High Doses ◽

And Function ◽

Type 3

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T3 to nuclear receptors. Brain T3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T4 and T3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

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Gene Expression Is Differentially Regulated in the Epididymis after Orchidectomy

Endocrinology ◽

10.1210/en.2002-220705 ◽

2003 ◽

Vol 144 (3) ◽

pp. 975-988 ◽

Cited By ~ 47

Author(s):

Nadine Ezer ◽

Bernard Robaire

Keyword(s):

Gene Expression ◽

Calcium Binding ◽

Regulation Of Gene Expression ◽

Brown Norway ◽

Norway Rat ◽

Associated Proteins ◽

Specific Regulation ◽

Cauda Epididymidis ◽

Shock Proteins ◽

And Function

The epididymis is the site for the transport, maturation, and storage of spermatozoa. Regulation of epididymal structure and function is highly dependent on the ipsilateral testis. At the molecular level, however, few studies have been undertaken to determine which genes are expressed in the epididymis under testicular regulation. The goal of this study was to identify genes for which expression is regulated after orchidectomy, both throughout the epididymis and in a segment-specific manner. Microarrays spotted with 474 rat cDNAs were used to examine gene expression changes over the first 7 d post orchidectomy in the initial segment, caput, corpus, and cauda epididymidis of the adult Brown Norway rat. Using k-means cluster analysis, we show that four patterns of gene expression are activated in each epididymal segment over the first week following orchidectomy. Transient up-regulation of gene expression in the epididymis after orchidectomy is described for the first time. Potential androgen-repressed genes, including Gpx-1, show increased expression in the epididymis after orchidectomy. Several glutathione-S-transferases and calcium-binding proteins decline throughout the epididymis after orchidectomy, indicating that these may be novel androgen-regulated epididymal genes. Other genes coding for metabolism-associated proteins, transporters, and α-1 acid glycoprotein show segment-specific regulation in the epididymis after orchidectomy. Finally, we describe the expression of the previously uncharacterized heat shock proteins, and apoptosis-associated genes in the epididymis after orchidectomy. Thus, gene expression in the epididymis is differentially affected over time after orchidectomy. These results provide novel insight into androgen-dependent and segment-specific epididymal function.

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Evolution of ageing as a tangle of trade-offs: energy versus function

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2019.1604 ◽

2019 ◽

Vol 286 (1911) ◽

pp. 20191604 ◽

Cited By ~ 10

Author(s):

Alexei A. Maklakov ◽

Tracey Chapman

Keyword(s):

Gene Expression ◽

Early Life ◽

Regulation Of Gene Expression ◽

Late Life ◽

Cellular Damage ◽

Future Research ◽

Relative Contribution ◽

Trade Offs ◽

Energy Trade ◽

And Function

Despite tremendous progress in recent years, our understanding of the evolution of ageing is still incomplete. A dominant paradigm maintains that ageing evolves due to the competing energy demands of reproduction and somatic maintenance leading to slow accumulation of unrepaired cellular damage with age. However, the centrality of energy trade-offs in ageing has been increasingly challenged as studies in different organisms have uncoupled the trade-off between reproduction and longevity. An emerging theory is that ageing instead is caused by biological processes that are optimized for early-life function but become harmful when they continue to run-on unabated in late life. This idea builds on the realization that early-life regulation of gene expression can break down in late life because natural selection is too weak to optimize it. Empirical evidence increasingly supports the hypothesis that suboptimal gene expression in adulthood can result in physiological malfunction leading to organismal senescence. We argue that the current state of the art in the study of ageing contradicts the widely held view that energy trade-offs between growth, reproduction, and longevity are the universal underpinning of senescence. Future research should focus on understanding the relative contribution of energy and function trade-offs to the evolution and expression of ageing.

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Genome-wide chromatin binding of transcriptional corepressor Topless-related 1 in Arabidopsis

10.1101/2020.04.25.060855 ◽

2020 ◽

Cited By ~ 1

Author(s):

Thomas Griebel ◽

Dmitry Lapin ◽

Barbara Kracher ◽

Lorenzo Concia ◽

Moussa Benhamed ◽

...

Keyword(s):

Gene Expression ◽

Regulation Of Gene Expression ◽

Plant Responses ◽

Dna Binding Domains ◽

Binding Domains ◽

Genome Wide ◽

Gene Expression Control ◽

Specific Regulation ◽

Transcriptional Corepressors ◽

And Function

AbstractTimely and specific regulation of gene expression is critical for plant responses to environmental and developmental cues. Transcriptional coregulators have emerged as important factors in gene expression control, although they lack DNA-binding domains and the mechanisms by which they are recruited to and function at the chromatin are poorly understood. Plant Topless-related 1 (TPR1), belonging to a family of transcriptional corepressors found across eukaryotes, contributes to immunity signaling in Arabidopsis thaliana and wild tobacco. We performed chromatin immunoprecipitation and sequencing (ChIP-seq) on an Arabidopsis TPR1-GFP expressing transgenic line to characterize genome-wide TPR1-chromatin associations. The analysis revealed ∼1400 genes bound by TPR1, with the majority of binding sites located at gene upstream regions. Among the TPR1 bound genes, we find not only regulators of immunity but also genes controlling growth and development. To support further analysis of TPR1-chromatin complexes and other transcriptional corepressors in plants, we provide two ways to access the processed ChIP-seq data and enable their broader use by the research community.

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NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states

Carcinogenesis ◽

10.1093/carcin/bgm200 ◽

2007 ◽

Vol 29 (1) ◽

pp. 2-8 ◽

Cited By ~ 114

Author(s):

T. P. Ellen ◽

Q. Ke ◽

P. Zhang ◽

M. Costa

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Regulation Of Gene Expression ◽

Related Gene ◽

Disease States ◽

Cancer Related Gene ◽

And Function

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MicroRNA biogenesis and variability

BioMolecular Concepts ◽

10.1515/bmc-2013-0015 ◽

2013 ◽

Vol 4 (4) ◽

pp. 367-380 ◽

Cited By ~ 21

Author(s):

Jesús García-López ◽

Miguel A. Brieño-Enríquez ◽

Jesús del Mazo

Keyword(s):

Gene Expression ◽

Posttranscriptional Regulation ◽

Regulation Of Gene Expression ◽

Noncoding Rnas ◽

High Variability ◽

Regulate Gene Expression ◽

Alternative Pathways ◽

Small Noncoding Rnas ◽

Fine Regulation ◽

And Function

AbstractMicroRNAs (miRNAs) are cell-endogenous small noncoding RNAs that, through RNA interference, are involved in the posttranscriptional regulation of mRNAs. The biogenesis and function of miRNAs entail multiple elements with different alternative pathways. These confer a high versatility of regulation and a high variability to generate different miRNAs and hence possess a broad potential to regulate gene expression. Here we review the different mechanisms, both canonical and noncanonical, that generate miRNAs in animals. The ‘miRNome’ panorama enhances our knowledge regarding the fine regulation of gene expression and provides new insights concerning normal, as opposed to pathological, cell differentiation and development.

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