International Journal of Molecular Sciences

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15 pages, 4837 KiB

Open AccessArticle

Distinct Patterns of GR Transcriptional Regulation in Liver and Muscle of LPS-Challenged Weaning Piglets

by Jie Liu, Yidan Jiang, Zheng Jiang, Yue Feng and Ruqian Zhao

Int. J. Mol. Sci. 2022, 23(15), 8072; https://doi.org/10.3390/ijms23158072 - 22 Jul 2022

Cited by 2 | Viewed by 1794

Abstract

Glucocorticoid receptor (GR), which is ubiquitously expressed in nearly all cell types of various organs, mediates the tissue-specific metabolic and immune responses to maintain homeostasis and ensure survival under stressful conditions or pathological challenges. The neonatal period is metabolically demanding, and piglets are [...] Read more.

Glucocorticoid receptor (GR), which is ubiquitously expressed in nearly all cell types of various organs, mediates the tissue-specific metabolic and immune responses to maintain homeostasis and ensure survival under stressful conditions or pathological challenges. The neonatal period is metabolically demanding, and piglets are subjected to multiple stressors in modern intensive farms, especially around weaning. The liver is more responsive to LPS challenge compared to muscle, which is indicated by significantly increased TLR4 and p-p65, TNF-α, and IL-6 levels in association with GR down-regulation at both mRNA and protein levels. GR binding to the putative nGRE on TNF-α and IL-6 gene promoters decreased in the liver, but not muscle, upon LPS stimulation. The transcriptional regulation of GR also showed striking differences between liver and muscle. GR exon 1 mRNA variants 1–4, 1–5, and 1–6 were down-regulated in both liver and muscle, but a significant up-regulation of GR exon 1–9/10 mRNA variants abolished the change of total GR mRNA in the muscle in response to LPS stimulation. The significant down-regulation of GR in the liver corresponded with significantly decreased binding of p-GR and diminished histone acetylation in GR gene promoters. These results indicate that tissue-specific GR transcriptional regulation is involved in the differential inflammation responses between liver and muscle. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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19 pages, 1945 KiB

Open AccessArticle

SMAD4 Feedback Activates the Canonical TGF-β Family Signaling Pathways

by Lu Liu, Qiqi Li, Liu Yang, Qifa Li and Xing Du

Int. J. Mol. Sci. 2021, 22(18), 10024; https://doi.org/10.3390/ijms221810024 - 16 Sep 2021

Cited by 18 | Viewed by 4832

Abstract

TGF-β family signaling pathways, including TGF-β and BMP pathways, are widely involved in the regulation of health and diseases through downstream SMADs, which are also regulated by multiple validated mechanisms, such as genetic regulation, epigenetic regulation, and feedback regulation. However, it is still [...] Read more.

TGF-β family signaling pathways, including TGF-β and BMP pathways, are widely involved in the regulation of health and diseases through downstream SMADs, which are also regulated by multiple validated mechanisms, such as genetic regulation, epigenetic regulation, and feedback regulation. However, it is still unclear whether R-SMADs or Co-SMAD can feedback regulate the TGF-β family signaling pathways in granulosa cells (GCs). In this study, we report a novel mechanism underlying the feedback regulation of TGF-β family signaling pathways, i.e., SMAD4, the only Co-SMAD, positive feedback activates the TGF-β family signaling pathways in GCs with a basal level of TGF-β ligands by interacting with the core promoters of its upstream receptors. Mechanistically, SMAD4 acts as a transcription factor, and feedback activates the transcription of its upstream receptors, including ACVR1B, BMPR2, and TGFBR2, of the canonical TGF-β signaling pathways by interacting with three coactivators (c-JUN, CREB1, and SP1), respectively. Notably, three different interaction modes between SMAD4 and coactivators were identified in SMAD4-mediated feedback regulation of upstream receptors through reciprocal ChIP assays. Our findings in the present study indicate for the first time that SMAD4 feedback activates the canonical TGF-β family signaling pathways in GCs, which improves and expands the regulatory mechanism, especially the feedback regulation modes of TGF-β family signaling pathways in ovarian GCs. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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15 pages, 2936 KiB

Open AccessArticle

The Connection between Czc and Cad Systems Involved in Cadmium Resistance in Pseudomonas putida

by Huizhong Liu, Yu Zhang, Yingsi Wang, Xiaobao Xie and Qingshan Shi

Int. J. Mol. Sci. 2021, 22(18), 9697; https://doi.org/10.3390/ijms22189697 - 8 Sep 2021

Cited by 14 | Viewed by 3055

Abstract

Heavy metal pollution is widespread and persistent, and causes serious harm to the environment. Pseudomonas putida, a representative environmental microorganism, has strong resistance to heavy metals due to its multiple efflux systems. Although the functions of many efflux systems have been well-studied, [...] Read more.

Heavy metal pollution is widespread and persistent, and causes serious harm to the environment. Pseudomonas putida, a representative environmental microorganism, has strong resistance to heavy metals due to its multiple efflux systems. Although the functions of many efflux systems have been well-studied, the relationship between them remains unclear. Here, the relationship between the Czc and Cad systems that are predominantly responsible for cadmium efflux in P. putida KT2440 is identified. The results demonstrated that CzcR3, the response regulator of two-component system CzcRS3 in the Czc system, activates the expression of efflux pump genes czcCBA1 and czcCBA2 by directly binding to their promoters, thereby helping the strain resist cadmium stress. CzcR3 can also bind to its own promoter, but it has only a weak regulatory effect. The high-level expression of czcRS3 needs to be induced by Cd²⁺, and this relies on the regulation of CadR, a key regulator in the Cad system, which showed affinity to czcRS3 promoter. Our study indicates that the Cad system is involved in the regulation of the Czc system, and this relationship is important for maintaining the considerable resistance to cadmium in P. putida. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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20 pages, 4579 KiB

Open AccessArticle

A Positive Regulatory Feedback Loop between EKLF/KLF1 and TAL1/SCL Sustaining the Erythropoiesis

by Chun-Hao Hung, Tung-Liang Lee, Anna Yu-Szu Huang, Kang-Chung Yang, Yu-Chiau Shyu, Shau-Ching Wen, Mu-Jie Lu, Shinsheng Yuan and Che-Kun James Shen

Int. J. Mol. Sci. 2021, 22(15), 8024; https://doi.org/10.3390/ijms22158024 - 27 Jul 2021

Cited by 3 | Viewed by 2703

Abstract

The erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to the CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and the promoter-based ChIP-chip assay of E14.5 fetal liver cells from [...] Read more.

The erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to the CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and the promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf^−/−) mouse embryos, we identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with the molecular/cellular analysis of the mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL, known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tal gene promoter in combination with the in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates the Tal gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors, which sustains mammalian erythropoiesis. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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17 pages, 3091 KiB

Open AccessArticle

Role of Methylation in Period2 (PER2) Transcription in the Context of the Presence or Absence of Light Signals: Natural and Chemical—Studies on the Pig Model

by Przemysław Gilun, Krzysztof Flisikowski, Tatiana Flisikowska, Joanna Kwiatkowska, Barbara Wąsowska and Magdalena Koziorowska-Gilun

Int. J. Mol. Sci. 2021, 22(15), 7796; https://doi.org/10.3390/ijms22157796 - 21 Jul 2021

Cited by 2 | Viewed by 2114

Abstract

It has been proposed that carbon monoxide (CO) is a chemical light carrier that is transferred by the humoral pathway from the retina to the brain. Here, we aimed to study how deeply CO is involved in regulating the expression of Period2 gene [...] Read more.

It has been proposed that carbon monoxide (CO) is a chemical light carrier that is transferred by the humoral pathway from the retina to the brain. Here, we aimed to study how deeply CO is involved in regulating the expression of Period2 gene (PER2), one of the genes maintaining the intrinsic biological clock. In our in vivo experiment, we studied whether CO may be a chemical signal and is also equivalent to natural light in three groups of pigs: Normal: housed in natural conditions without any procedures, Control: adapted and kept in constant darkness, infused with blank plasma, and CO treated: adapted and kept in constant darkness infused with CO-enriched plasma. After the experiment, the animals were slaughtered at two times of day: 12 p.m. and 12 a.m. Next, hypothalamus samples were collected. Quantitative PCR, the DNA methylation of the promoter sequence containing enhancers (E-box) and a functional analysis of the PER2 promoter was performed. qPCR showed a differential pattern of PER2 mRNA expression at daytime oscillation in the examined groups. Pyrosequencing revealed daytime changes in the methylation level of regulatory sites of the examined sequence. Luciferase reporter assay confirmed that E-boxes (CANNTG) drive the expression of the porcine PER2 in vitro. In conclusion, changes in methylation over 24 h may regulate the oscillatory manner of PER2 expression. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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17 pages, 3381 KiB

Open AccessArticle

DNA G-Quadruplexes Contribute to CTCF Recruitment

by Polina Tikhonova, Iulia Pavlova, Ekaterina Isaakova, Vladimir Tsvetkov, Alexandra Bogomazova, Tatjana Vedekhina, Artem V. Luzhin, Rinat Sultanov, Vjacheslav Severov, Ksenia Klimina, Omar L. Kantidze, Galina Pozmogova, Maria Lagarkova and Anna Varizhuk

Int. J. Mol. Sci. 2021, 22(13), 7090; https://doi.org/10.3390/ijms22137090 - 30 Jun 2021

Cited by 13 | Viewed by 5016

Abstract

G-quadruplex (G4) sites in the human genome frequently colocalize with CCCTC-binding factor (CTCF)-bound sites in CpG islands (CGIs). We aimed to clarify the role of G4s in CTCF positioning. Molecular modeling data suggested direct interactions, so we performed in vitro binding assays with [...] Read more.

G-quadruplex (G4) sites in the human genome frequently colocalize with CCCTC-binding factor (CTCF)-bound sites in CpG islands (CGIs). We aimed to clarify the role of G4s in CTCF positioning. Molecular modeling data suggested direct interactions, so we performed in vitro binding assays with quadruplex-forming sequences from CGIs in the human genome. G4s bound CTCF with Kd values similar to that of the control duplex, while respective i-motifs exhibited no affinity for CTCF. Using ChIP-qPCR assays, we showed that G4-stabilizing ligands enhance CTCF occupancy at a G4-prone site in STAT3 gene. In view of the reportedly increased CTCF affinity for hypomethylated DNA, we next questioned whether G4s also facilitate CTCF recruitment to CGIs via protecting CpG sites from methylation. Bioinformatics analysis of previously published data argued against such a possibility. Finally, we questioned whether G4s facilitate CTCF recruitment by affecting chromatin structure. We showed that three architectural chromatin proteins of the high mobility group colocalize with G4s in the genome and recognize parallel-stranded or mixed-topology G4s in vitro. One of such proteins, HMGN3, contributes to the association between G4s and CTCF according to our bioinformatics analysis. These findings support both direct and indirect roles of G4s in CTCF recruitment. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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12 pages, 2490 KiB

Open AccessArticle

by Guanwang Shen, Jinxin Wu, Ying Lin, Xiaoting Hua, Qingyou Xia and Ping Zhao

Int. J. Mol. Sci. 2021, 22(9), 4343; https://doi.org/10.3390/ijms22094343 - 21 Apr 2021

Cited by 9 | Viewed by 2509

Abstract

The expression of trehalase in the midgut of insects plays an important role in glucose supply to the hemolymph. Energy metabolism is usually regulated by the estrogen-related receptor (ERR). A decrease in ATP levels is caused by the ERR hindering glycolysis. However, the [...] Read more.

The expression of trehalase in the midgut of insects plays an important role in glucose supply to the hemolymph. Energy metabolism is usually regulated by the estrogen-related receptor (ERR). A decrease in ATP levels is caused by the ERR hindering glycolysis. However, the relationship between trehalose accumulation and ERR expression is still unclear. Here, we found that silkworm ERR (BmERR) is concentrated and BmERR expression is strongly correlated with trehalase in the midgut during the last instar silkworm larval stage. We cloned the promoter of the trehalase from Bombyx mori (BmTreh) and found that the ERR bound directly to the core response elements of the promoter. Cell level interference and the overexpression of ERR can reduce or enhance BmTreh transcription and promoter activity. Overexpressed transgenic BmERR can significantly increase the expression of BmTreh in the midgut of the last instar silkworm larvae, thereby hydrolyzing trehalose into glucose and releasing it into the hemolymph. Additionally, increased hemolymph glucose content reduces silkworm pupa weight but does not affect silk protein production from the silk gland. Our results suggest a novel function for BmERR through its involvement in BmTreh regulation and expand the understanding of ERR functions in insect trehalose metabolism. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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14 pages, 4133 KiB

Open AccessArticle

ATF3 Promotes Arsenic-Induced Apoptosis and Oppositely Regulates DR5 and Bcl-xL Expression in Human Bronchial Epithelial Cells

by Qiwen Shi, Bei Hu, Chen Yang, Lan Zhao, Jing Wu and Nan Qi

Int. J. Mol. Sci. 2021, 22(8), 4223; https://doi.org/10.3390/ijms22084223 - 19 Apr 2021

Cited by 16 | Viewed by 2583

Abstract

Arsenic is one of the most common environmental pollutants eliciting serious public health issues; however, it is also a well-recognized chemotherapeutic agent for acute promyelocytic leukemia. The association between arsenic exposure and lung diseases has been established, but underlying molecular mechanisms are poorly [...] Read more.

Arsenic is one of the most common environmental pollutants eliciting serious public health issues; however, it is also a well-recognized chemotherapeutic agent for acute promyelocytic leukemia. The association between arsenic exposure and lung diseases has been established, but underlying molecular mechanisms are poorly defined. Here we investigated the toxicology of arsenic in airway epithelium. Arsenic rapidly induced the activating transcription factor ATF3 expression through the JNK and p38 pathways. The ATF3-deficient BEAS-2B cells were relatively resistant to apoptosis upon arsenic exposure, indicating a facilitatory role of ATF3 in arsenic-induced apoptosis. We further showed that ATF3 oppositely regulated the transcription of death receptor (DR5) and Bcl2-like 1 (Bcl-xL) by directly binding to the promoter DR5 and Bcl-xL. Altogether, our findings establish ATF3 as a pro-apoptotic protein in arsenic-induced airway epithelial apoptosis through transcriptionally regulating DR5 and Bcl-xL, highlighting the potential of ATF3 as an early and sensitive biomarker for arsenic-caused lung injury. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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16 pages, 3301 KiB

Open AccessArticle

Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats

by Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Kana Shimizu, Yusuke Miyazaki, Nurmila Sari, Satoshi Shimizu, Kiyoshi Mori, Hiromichi Wada, Koji Hasegawa and Tatsuya Morimoto

Int. J. Mol. Sci. 2021, 22(4), 1771; https://doi.org/10.3390/ijms22041771 - 10 Feb 2021

Cited by 19 | Viewed by 3286

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

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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32 pages, 5542 KiB

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

by Karolina Jaworska, Marta Ludwiczak, Emilia Murawska, Adrianna Raczkowska and Katarzyna Brzostek

Int. J. Mol. Sci. 2021, 22(3), 1475; https://doi.org/10.3390/ijms22031475 - 2 Feb 2021

Cited by 4 | Viewed by 3723

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

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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24 pages, 5074 KiB

Open AccessArticle

A Novel Multiprotein Bridging Factor 1-Like Protein Induces Cyst Wall Protein Gene Expression and Cyst Differentiation in Giardia lamblia

by Shao-Wei Huang, Zi-Qi Lin, Szu-Yu Tung, Li-Hsin Su, Chun-Che Ho, Gilbert Aaron Lee and Chin-Hung Sun

Int. J. Mol. Sci. 2021, 22(3), 1370; https://doi.org/10.3390/ijms22031370 - 29 Jan 2021

Cited by 6 | Viewed by 2580

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

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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17 pages, 4885 KiB

Open AccessArticle

TRIM28 Regulates Dlk1 Expression in Adipogenesis

by Hsin-Pin Lu, Chieh-Ju Lin, Wen-Ching Chen, Yao-Jen Chang, Sheng-Wei Lin, Hsin-Hui Wang and Ching-Jin Chang

Int. J. Mol. Sci. 2020, 21(19), 7245; https://doi.org/10.3390/ijms21197245 - 30 Sep 2020

Cited by 8 | Viewed by 3854

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

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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17 pages, 3037 KiB

Open AccessArticle

F-Box Gene D5RF Is Regulated by Agrobacterium Virulence Protein VirD5 and Essential for Agrobacterium-Mediated Plant Transformation

by Shaojuan Zhang, Zhuo Chen, Fei Huang, Yafei Wang and Meizhong Luo

Int. J. Mol. Sci. 2020, 21(18), 6731; https://doi.org/10.3390/ijms21186731 - 14 Sep 2020

Cited by 2 | Viewed by 2719

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

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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Review

Jump to: Research

13 pages, 1040 KiB

Open AccessReview

Enhancer-Mediated Formation of Nuclear Transcription Initiation Domains

by Matthew D. Gibbons, Yu Fang, Austin P. Spicola, Niko Linzer, Stephen M. Jones, Breanna R. Johnson, Lu Li, Mingyi Xie and Jörg Bungert

Int. J. Mol. Sci. 2022, 23(16), 9290; https://doi.org/10.3390/ijms23169290 - 18 Aug 2022

Cited by 5 | Viewed by 3523

Abstract

Enhancers in higher eukaryotes and upstream activating sequences (UASs) in yeast have been shown to recruit components of the RNA polymerase II (Pol II) transcription machinery. At least a fraction of Pol II recruited to enhancers in higher eukaryotes initiates transcription and generates [...] Read more.

Enhancers in higher eukaryotes and upstream activating sequences (UASs) in yeast have been shown to recruit components of the RNA polymerase II (Pol II) transcription machinery. At least a fraction of Pol II recruited to enhancers in higher eukaryotes initiates transcription and generates enhancer RNA (eRNA). In contrast, UASs in yeast do not recruit transcription factor TFIIH, which is required for transcription initiation. For both yeast and mammalian systems, it was shown that Pol II is transferred from enhancers/UASs to promoters. We propose that there are two modes of Pol II recruitment to enhancers in higher eukaryotes. Pol II complexes that generate eRNAs are recruited via TFIID, similar to mechanisms operating at promoters. This may involve the binding of TFIID to acetylated nucleosomes flanking the enhancer. The resulting eRNA, together with enhancer-bound transcription factors and co-regulators, contributes to the second mode of Pol II recruitment through the formation of a transcription initiation domain. Transient contacts with target genes, governed by proteins and RNA, lead to the transfer of Pol II from enhancers to TFIID-bound promoters. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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15 pages, 857 KiB

Open AccessReview

Towards an Ideal In Cell Hybridization-Based Strategy to Discover Protein Interactomes of Selected RNA Molecules

by Michele Spiniello, Mark Scalf, Amelia Casamassimi, Ciro Abbondanza and Lloyd M. Smith

Int. J. Mol. Sci. 2022, 23(2), 942; https://doi.org/10.3390/ijms23020942 - 15 Jan 2022

Viewed by 1772

Abstract

RNA-binding proteins are crucial to the function of coding and non-coding RNAs. The disruption of RNA–protein interactions is involved in many different pathological states. Several computational and experimental strategies have been developed to identify protein binders of selected RNA molecules. Amongst these, ‘ [...] Read more.

RNA-binding proteins are crucial to the function of coding and non-coding RNAs. The disruption of RNA–protein interactions is involved in many different pathological states. Several computational and experimental strategies have been developed to identify protein binders of selected RNA molecules. Amongst these, ‘in cell’ hybridization methods represent the gold standard in the field because they are designed to reveal the proteins bound to specific RNAs in a cellular context. Here, we compare the technical features of different ‘in cell’ hybridization approaches with a focus on their advantages, limitations, and current and potential future applications. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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25 pages, 3231 KiB

Open AccessReview

Functional Amino Acids and Autophagy: Diverse Signal Transduction and Application

by Chunchen Liu, Linbao Ji, Jinhua Hu, Ying Zhao, Lee J. Johnston, Xiujun Zhang and Xi Ma

Int. J. Mol. Sci. 2021, 22(21), 11427; https://doi.org/10.3390/ijms222111427 - 22 Oct 2021

Cited by 14 | Viewed by 6675

Abstract

Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated [...] Read more.

Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated with various diseases, such as cancer, neurodegeneration, aging, and obesity. Autophagy cannot be directly controlled and dynamic amino acid levels are sufficient to regulate autophagy. To date, arginine, leucine, glutamine, and methionine are widely reported functional amino acids that regulate autophagy. As a signal relay station, mammalian target of rapamycin complex 1 (mTORC1) turns various amino acid signals into autophagy signaling pathways for functional amino acids. Deficiency or supplementation of functional amino acids can immediately regulate autophagy and is associated with autophagy-related disease. This review summarizes the mechanisms currently involved in autophagy and amino acid sensing, diverse signal transduction among functional amino acids and autophagy, and the therapeutic appeal of amino acids to autophagy-related diseases. We aim to provide a comprehensive overview of the mechanisms of amino acid regulation of autophagy and the role of functional amino acids in clinical autophagy-related diseases and to further convert these mechanisms into feasible therapeutic applications. Full article

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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24 pages, 4558 KiB

Open AccessReview

Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery

by Ryan D. Martin, Terence E. Hébert and Jason C. Tanny

Int. J. Mol. Sci. 2020, 21(9), 3354; https://doi.org/10.3390/ijms21093354 - 9 May 2020

Cited by 31 | Viewed by 7878

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

(This article belongs to the Special Issue Transcriptional Regulation: Molecules, Involved Mechanisms and Misregulation)

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