Transcriptional control of maladaptive and protective responses in alcoholics: A role of the NF-κB system

AbstractThe estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.

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The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

10.1101/2020.07.15.204107 ◽

2020 ◽

Author(s):

Joanna Houghton ◽

Angela Rodgers ◽

Graham Rose ◽

Kristine B. Arnvig

Keyword(s):

Gene Expression ◽

Mycobacterium Tuberculosis ◽

Small Rnas ◽

Transcriptional Control ◽

Cold Shock ◽

Control Of Gene Expression ◽

Rna Biology ◽

Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

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Transcriptional Control of Honey Bee (Apis mellifera) Major Royal Jelly Proteins by 20-Hydroxyecdysone

Insects ◽

10.3390/insects9030122 ◽

2018 ◽

Vol 9 (3) ◽

pp. 122 ◽

Cited By ~ 4

Author(s):

Paul Winkler ◽

Frank Sieg ◽

Anja Buttstedt

Keyword(s):

Gene Expression ◽

Apis Mellifera ◽

Juvenile Hormone ◽

Honey Bee ◽

Honey Bees ◽

Transcriptional Control ◽

Royal Jelly ◽

Adult Worker ◽

Gene Expression Dynamics

One of the first tasks of worker honey bees (Apis mellifera) during their lifetime is to feed the larval offspring. In brief, young workers (nurse bees) secrete a special food jelly that contains a large amount of unique major royal jelly proteins (MRJPs). The regulation of mrjp gene expression is not well understood, but the large upregulation in well-fed nurse bees suggests a tight repression until, or a massive induction upon, hatching of the adult worker bees. The lipoprotein vitellogenin, the synthesis of which is regulated by the two systemic hormones 20-hydroxyecdysone and juvenile hormone, is thought to be a precursor for the production of MRJPs. Thus, the regulation of mrjp expression by the said systemic hormones is likely. This study focusses on the role of 20-hydroxyecdysone by elucidating its effect on mrjp gene expression dynamics. Specifically, we tested whether 20-hydroxyecdysone displayed differential effects on various mrjps. We found that the expression of the mrjps (mrjp1–3) that were finally secreted in large amounts into the food jelly, in particular, were down regulated by 20-hydroxyecdysone treatment, with mrjp3 showing the highest repression value.

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Epigenetic regulation of adipogenesis by histone-modifying enzymes

Epigenomics ◽

10.2217/epi-2020-0304 ◽

2021 ◽

Vol 13 (3) ◽

pp. 235-251

Author(s):

Paolo E Macchia ◽

Immacolata C Nettore ◽

Fabiana Franchini ◽

Laura Santana-Viera ◽

Paola Ungaro

Keyword(s):

Epigenetic Regulation ◽

Transcriptional Control ◽

Metabolic Diseases ◽

Epigenetic Mechanisms ◽

Differentiation Process ◽

Histone Tails ◽

Histone Modifying Enzymes ◽

Epigenomic Regulation ◽

Adipocyte Development

Many studies investigating the transcriptional control of adipogenesis have been published so far; recently the research is focusing on the role of epigenetic mechanisms in regulating the process of adipocyte development. Histone-modifying enzymes and the histone tails post-transcriptional modifications catalyzed by them, are fundamentally involved in the epigenetic regulation of adipogenesis. In our review, we will discuss recent advances in epigenomic regulation of adipogenesis with a focus on histone-modifying enzymes implicated in the various phases of adipocytes differentiation process from mesenchymal stem cells to mature adipocytes. Understanding adipogenesis, may provide new ways to treat obesity and related metabolic diseases.

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Role of Histone Deacetylases in Transcriptional Control of the Hepatic Stellate Cell Phenotype

Extracellular Matrix and the Liver ◽

10.1016/b978-012525251-5/50012-9 ◽

2003 ◽

pp. 189-205

Author(s):

Krista Rombouts ◽

Toshiro Niki ◽

Minura Yoshida ◽

Albert Geerts

Keyword(s):

Hepatic Stellate Cell ◽

Histone Deacetylases ◽

Transcriptional Control ◽

Stellate Cell ◽

Cell Phenotype

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“What You Need, Baby, I Got It”: Transposable Elements as Suppliers of Cis-Operating Sequences in Drosophila

Biology ◽

10.3390/biology9020025 ◽

2020 ◽

Vol 9 (2) ◽

pp. 25 ◽

Cited By ~ 1

Author(s):

Roberta Moschetti ◽

Antonio Palazzo ◽

Patrizio Lorusso ◽

Luigi Viggiano ◽

René Massimiliano Marsano

Keyword(s):

Transposable Elements ◽

Transcriptional Control ◽

Environmental Changes ◽

Model Organism ◽

Model Organisms ◽

Regulatory Sequences ◽

Transcriptional Pattern ◽

Constitutive Components ◽

Host Genes

Transposable elements (TEs) are constitutive components of both eukaryotic and prokaryotic genomes. The role of TEs in the evolution of genes and genomes has been widely assessed over the past years in a variety of model and non-model organisms. Drosophila is undoubtedly among the most powerful model organisms used for the purpose of studying the role of transposons and their effects on the stability and evolution of genes and genomes. Besides their most intuitive role as insertional mutagens, TEs can modify the transcriptional pattern of host genes by juxtaposing new cis-regulatory sequences. A key element of TE biology is that they carry transcriptional control elements that fine-tune the transcription of their own genes, but that can also perturb the transcriptional activity of neighboring host genes. From this perspective, the transposition-mediated modulation of gene expression is an important issue for the short-term adaptation of physiological functions to the environmental changes, and for long-term evolutionary changes. Here, we review the current literature concerning the regulatory and structural elements operating in cis provided by TEs in Drosophila. Furthermore, we highlight that, besides their influence on both TEs and host genes expression, they can affect the chromatin structure and epigenetic status as well as both the chromosome’s structure and stability. It emerges that Drosophila is a good model organism to study the effect of TE-linked regulatory sequences, and it could help future studies on TE–host interactions in any complex eukaryotic genome.

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Role of the FliA-FlgM regulatory system on the transcriptional control of the flagellar regulon and flagellar formation in Salmonella typhimurium.

Journal of Bacteriology ◽

10.1128/jb.176.12.3598-3605.1994 ◽

1994 ◽

Vol 176 (12) ◽

pp. 3598-3605 ◽

Cited By ~ 111

Author(s):

K Kutsukake ◽

T Iino

Keyword(s):

Salmonella Typhimurium ◽

Transcriptional Control ◽

Regulatory System ◽

Flagellar Regulon

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Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis

International Journal of Molecular Sciences ◽

10.3390/ijms20123073 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3073 ◽

Cited By ~ 3

Author(s):

Ana Dienstbier ◽

Fabian Amman ◽

Daniel Štipl ◽

Denisa Petráčková ◽

Branislav Večerek

Keyword(s):

Gene Expression ◽

Bordetella Pertussis ◽

Transcriptional Control ◽

Whooping Cough ◽

Expression Profiles ◽

Bacterial Pathogen ◽

Gene Expression Profiles ◽

Control Of Gene Expression ◽

Proteomic Data

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r2 = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene.

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Post-Translational Modification-Dependent Activity of Matrix Metalloproteinases

International Journal of Molecular Sciences ◽

10.3390/ijms20123077 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3077 ◽

Cited By ~ 10

Author(s):

Elizabeta Madzharova ◽

Philipp Kastl ◽

Fabio Sabino ◽

Ulrich auf dem Keller

Keyword(s):

Matrix Metalloproteinases ◽

Transcriptional Control ◽

Proteolytic Processing ◽

Post Translational Modification ◽

Proteolytic Activation ◽

Control Of Gene Expression ◽

Post Translational Modifications ◽

Binding Partners ◽

Secreted Proteases

Due to their capacity to process different proteins of the extracellular matrix (ECM), matrix metalloproteinases (MMPs) were initially described as a family of secreted proteases, functioning as main ECM regulators. However, through proteolytic processing of various biomolecules, MMPs also modulate intra- and extracellular pathways and networks. Thereby, they are functionally implicated in the regulation of multiple physiological and pathological processes. Consequently, MMP activity is tightly regulated through a combination of epigenetic, transcriptional, and post-transcriptional control of gene expression, proteolytic activation, post-translational modifications (PTMs), and extracellular inhibition. In addition, MMPs, their substrates and ECM binding partners are frequently modified by PTMs, which suggests an important role of PTMs in modulating the pleiotropic activities of these proteases. This review summarizes the recent progress towards understanding the role of PTMs (glycosylation, phosphorylation, glycosaminoglycans) on the activity of several members of the MMP family.

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