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Topical Collection "Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation"

A topical collection in International Journal of Molecular Sciences (ISSN 1422-0067). This collection belongs to the section "Molecular Biology".

Editor

Topical Collection Information

Dear colleagues,

Transcriptional regulation of gene expression in response to intra- and extracellular changes includes a series of biophysical processes controlled by innumerable transcription factors, cofactors, and chromatin regulators. This control involves multiple temporal and functional steps and levels, ranging from specific DNA–protein interactions to the recruitment and assembly of nucleoprotein complexes. The huge number of participating molecules, together with the complexity of the mechanisms, constrains the use of novel strategies to fully understand how DNA sequence information, epigenetic modifications, and transcription machinery cooperate to regulate gene expression. Recent advances in “omics” and computational biology have provided promising tools to reliably integrate different layers of information from biophysical, biochemical, and molecular cell biology studies. Thus, this Topical Collection is focused on the molecular mechanisms leading to specific gene expression patterns, with particular attention to molecules and complexes involved in transcription regulation. In particular, studies employing these novel integrated approaches will be prioritized. Additionally, research papers and review articles exploring the effects of transcriptional misregulation on human diseases are also of interest.

Dr. Amelia Casamassimi
Guest Editor

Manuscript Submission Information

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Keywords

  • transcription machinery
  • nucleic acid-protein interactions
  • chromatin modifying complexes
  • molecular recognition
  • biomolecular interactions
  • posttranscriptional modifications
  • transcription misregulation
  • computational biophysics

Published Papers (6 papers)

2021

Jump to: 2020

Open AccessArticle
Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats
Int. J. Mol. Sci. 2021, 22(4), 1771; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041771 - 10 Feb 2021
Abstract
Histone acetylation by epigenetic regulators has been shown to activate the transcription of hypertrophic response genes, which subsequently leads to the development and progression of heart failure. However, nothing is known about the acetylation of the histone tail and globular domains in left [...] Read more.
Histone acetylation by epigenetic regulators has been shown to activate the transcription of hypertrophic response genes, which subsequently leads to the development and progression of heart failure. However, nothing is known about the acetylation of the histone tail and globular domains in left ventricular hypertrophy or in heart failure. The acetylation of H3K9 on the promoter of the hypertrophic response gene was significantly increased in the left ventricular hypertrophy stage, whereas the acetylation of H3K122 did not increase in the left ventricular hypertrophy stage but did significantly increase in the heart failure stage. Interestingly, the interaction between the chromatin remodeling factor BRG1 and p300 was significantly increased in the heart failure stage, but not in the left ventricular hypertrophy stage. This study demonstrates that stage-specific acetylation of the histone tail and globular domains occurs during the development and progression of heart failure, providing novel insights into the epigenetic regulatory mechanism governing transcriptional activity in these processes. Full article
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Open AccessArticle
The Regulator OmpR in Yersinia enterocolitica Participates in Iron Homeostasis by Modulating Fur Level and Affecting the Expression of Genes Involved in Iron Uptake
Int. J. Mol. Sci. 2021, 22(3), 1475; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031475 - 02 Feb 2021
Abstract
In this study, we found that the loss of OmpR, the response regulator of the two-component EnvZ/OmpR system, increases the cellular level of Fur, the master regulator of iron homeostasis in Y. enterocolitica. Furthermore, we demonstrated that transcription of the fur gene [...] Read more.
In this study, we found that the loss of OmpR, the response regulator of the two-component EnvZ/OmpR system, increases the cellular level of Fur, the master regulator of iron homeostasis in Y. enterocolitica. Furthermore, we demonstrated that transcription of the fur gene from the YePfur promoter is subject to negative OmpR-dependent regulation. Four putative OmpR-binding sites (OBSs) were indicated by in silico analysis of the fur promoter region, and their removal affected OmpR-dependent fur expression. Moreover, OmpR binds specifically to the predicted OBSs which exhibit a distinct hierarchy of binding affinity. Finally, the data demonstrate that OmpR, by direct binding to the promoters of the fecA, fepA and feoA genes, involved in the iron transport and being under Fur repressor activity, modulates their expression. It seems that the negative effect of OmpR on fecA and fepA transcription is sufficient to counteract the indirect, positive effect of OmpR resulting from decreasing the Fur repressor level. The expression of feoA was positively regulated by OmpR and this mode of action seems to be direct and indirect. Together, the expression of fecA, fepA and feoA in Y. enterocolitica has been proposed to be under a complex mode of regulation involving OmpR and Fur regulators. Full article
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Open AccessArticle
A Novel Multiprotein Bridging Factor 1-Like Protein Induces Cyst Wall Protein Gene Expression and Cyst Differentiation in Giardia lamblia
Int. J. Mol. Sci. 2021, 22(3), 1370; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031370 - 29 Jan 2021
Abstract
The capacity to synthesize a protective cyst wall is critical for infectivity of Giardia lamblia. It is of interest to know the mechanism of coordinated synthesis of three cyst wall proteins (CWPs) during encystation, a differentiation process. Multiprotein bridging factor 1 (MBF1) [...] Read more.
The capacity to synthesize a protective cyst wall is critical for infectivity of Giardia lamblia. It is of interest to know the mechanism of coordinated synthesis of three cyst wall proteins (CWPs) during encystation, a differentiation process. Multiprotein bridging factor 1 (MBF1) gene family is a group of transcription coactivators that bridge various transcription factors. They are involved in cell growth and differentiation in yeast and animals, or in stress response in fungi and plants. We asked whether Giardia has MBF1-like genes and whether their products influence gene expression. BLAST searches of the Giardia genome database identified one gene encoding a putative MBF1 protein with a helix-turn-helix domain. We found that it can specifically bind to the AT-rich initiator promoters of the encystation-induced cwp1-3 and myb2 genes. MBF1 localized to cell nuclei and cytoplasm with higher expression during encystation. In addition, overexpression of MBF1 induced cwp1-3 and myb2 gene expression and cyst generation. Mutation of the helixes in the helix-turn-helix domain reduced cwp1-3 and myb2 gene expression and cyst generation. Chromatin immunoprecipitation assays confirmed the binding of MBF1 to the promoters with its binding sites in vivo. We also found that MBF1 can interact with E2F1, Pax2, WRKY, and Myb2 transcription factors that coordinately up-regulate the cwp genes during encystation. Using a CRISPR/Cas9 system for targeted disruption of mbf1 gene, we found a downregulation of cwp1-3 and myb2 genes and decrease of cyst generation. Our results suggest that MBF1 is functionally conserved and positively regulates Giardia cyst differentiation. Full article
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2020

Jump to: 2021

Open AccessArticle
TRIM28 Regulates Dlk1 Expression in Adipogenesis
Int. J. Mol. Sci. 2020, 21(19), 7245; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197245 - 30 Sep 2020
Abstract
The tripartite motif-containing protein 28 (TRIM28) is a transcription corepressor, interacting with histone deacetylase and methyltransferase complexes. TRIM28 is a crucial regulator in development and differentiation. We would like to investigate its function and regulation in adipogenesis. Knockdown of Trim28 by transducing lentivirus-carrying [...] Read more.
The tripartite motif-containing protein 28 (TRIM28) is a transcription corepressor, interacting with histone deacetylase and methyltransferase complexes. TRIM28 is a crucial regulator in development and differentiation. We would like to investigate its function and regulation in adipogenesis. Knockdown of Trim28 by transducing lentivirus-carrying shRNAs impairs the differentiation of 3T3-L1 preadipocytes, demonstrated by morphological observation and gene expression analysis. To understand the molecular mechanism of Trim28-mediated adipogenesis, the RNA-seq was performed to find out the possible Trim28-regulated genes. Dlk1 (delta-like homolog 1) was increased in Trim28 knockdown 3T3-L1 cells both untreated and induced to differentiation. Dlk1 is an imprinted gene and known as an inhibitor of adipogenesis. Further knockdown of Dlk1 in Trim28 knockdown 3T3-L1 would rescue cell differentiation. The epigenetic analysis showed that DNA methylation of Dlk1 promoter and differentially methylated regions (DMRs) was not altered significantly in Trim28 knockdown cells. However, compared to control cells, the histone methylation on the Dlk1 promoter was increased at H3K4 and decreased at H3K27 in Trim28 knockdown cells. Finally, we found Trim28 might be recruited by transcription factor E2f1 to regulate Dlk1 expression. The results imply Trim28-Dlk1 axis is critical for adipogenesis. Full article
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Open AccessArticle
F-Box Gene D5RF Is Regulated by Agrobacterium Virulence Protein VirD5 and Essential for Agrobacterium-Mediated Plant Transformation
Int. J. Mol. Sci. 2020, 21(18), 6731; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186731 - 14 Sep 2020
Abstract
We previously reported that the Agrobacterium virulence protein VirD5 possesses transcriptional activation activity, binds to a specific DNA element D5RE, and is required for Agrobacterium-mediated stable transformation, but not for transient transformation. However, direct evidence for a role of VirD5 in plant [...] Read more.
We previously reported that the Agrobacterium virulence protein VirD5 possesses transcriptional activation activity, binds to a specific DNA element D5RE, and is required for Agrobacterium-mediated stable transformation, but not for transient transformation. However, direct evidence for a role of VirD5 in plant transcriptional regulation has been lacking. In this study, we found that the Arabidopsis gene D5RF (coding for VirD5 response F-box protein, At3G49480) is regulated by VirD5. D5RF has two alternative transcripts of 930 bp and 1594 bp that encode F-box proteins of 309 and 449 amino acids, designated as D5RF.1 and D5RF.2, respectively. D5RF.2 has a N-terminal extension of 140 amino acids compared to D5RF.1, and both of them are located in the plant cell nucleus. The promoter of the D5RF.1 contains two D5RE elements and can be activated by VirD5. The expression of D5RF is downregulated when the host plant is infected with virD5 deleted Agrobacterium. Similar to VirD5, D5RF also affects the stable but not transient transformation efficiency of Agrobacterium. Some pathogen-responsive genes are downregulated in the d5rf mutant. In conclusion, this study further confirmed Agrobacterium VirD5 as the plant transcription activator and identified Arabidopsis thalianaD5RF.1 as the first target gene of VirD5 in regulation. Full article
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Open AccessReview
Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery
Int. J. Mol. Sci. 2020, 21(9), 3354; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093354 - 09 May 2020
Cited by 2
Abstract
Inhibitors targeting the general RNA polymerase II (RNAPII) transcription machinery are candidate therapeutics in cancer and other complex diseases. Here, we review the molecular targets and mechanisms of action of these compounds, framing them within the steps of RNAPII transcription. We discuss the [...] Read more.
Inhibitors targeting the general RNA polymerase II (RNAPII) transcription machinery are candidate therapeutics in cancer and other complex diseases. Here, we review the molecular targets and mechanisms of action of these compounds, framing them within the steps of RNAPII transcription. We discuss the effects of transcription inhibitors in vitro and in cellular models (with an emphasis on cancer), as well as their efficacy in preclinical and clinical studies. We also discuss the rationale for inhibiting broadly acting transcriptional regulators or RNAPII itself in complex diseases. Full article
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