Regulation of Ci-tropomyosin-like, a Brachyury target gene in the ascidian, Ciona intestinalis

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5599-5609 ◽  
Author(s):  
A. Di Gregorio ◽  
M. Levine
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Ciona Intestinalis ◽  
Subtractive Hybridization ◽  
Flanking Sequence ◽  
Binding Assays ◽  
Specific Staining ◽  
Direct Target Gene ◽  
Direct Target

Brachyury is a sequence-specific transcriptional activator that is essential for notochord differentiation in a variety of chordates. In vertebrates, Brachyury is expressed throughout the presumptive mesoderm, but becomes restricted to the notochord at later stages of development. In ascidians, such as Ciona intestinalis, Brachyury is expressed exclusively in the notochord and does not exhibit an early pan-mesodermal pattern. Subtractive hybridization screens were recently used to identify potential Ciona Brachyury (Ci-Bra) target genes (Takahashi, H., Hotta, K., Erives, A., Di Gregorio, A., Zeller, R. W., Levine, M. and Satoh, N. (1999). Genes Dev. 13, 1519–1523). Of the genes that were identified in this screen, one corresponds to a new member of the tropomyosin superfamily, Ciona tropomyosin (Ci-trop). Here we show that Ci-trop is specifically expressed in the developing notochord beginning at gastrulation, and expression persists in the notochord during tailbud and tadpole stages. A 3 kb region of the Ci-trop 5′-flanking sequence was characterized via electroporation of lacZ fusion genes into fertilized Ciona eggs. A minimal, 114 bp enhancer was identified that is sufficient to direct the expression of a heterologous promoter in the notochord. DNA binding assays indicate that this enhancer contains two sets of low-affinity Brachyury half-sites, which are bound in vitro by a GST/Ci-Bra fusion protein. Deletion of the distal sites inactivates the notochord-specific staining pattern mediated by an otherwise normal Ci-trop/lacZ transgene. These results suggest that Ci-trop is a direct target gene of Ci-Bra and that Brachyury plays an immediate role in the cellular morphogenesis of the notochord.

scholarly journals MiR-429 Determines Poor Outcome and Inhibits Pancreatic Ductal Adenocarcinoma Growth by Targeting TBK1

2015 ◽  
Vol 35 (5) ◽  
pp. 1846-1856 ◽  
Author(s):  
Bin Song ◽  
Kailian Zheng ◽  
Hongyun Ma ◽  
Anan Liu ◽  
Wei Jing ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Target Gene ◽  
Target Genes ◽  
Ductal Adenocarcinoma ◽  
Direct Target Gene ◽  
Direct Target ◽  
Sw1990 Cell ◽  
High Level

Background: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death and its prognosis has not improved significantly over the past decades. Deregulation or dysfunction of miRNAs contribute to cancer development. Previous data indicates that miR-429 is involved in the pathogenesis of PDAC. However, the role of miR-429 in PDAC remained unknown. Methods: MiR-429 levels in sample tissues of 78 patients and in PANC1 and SW1990 cell lines were quantified by real-time PCR. MiR-429 expression was modulated using specific pre- and anti-miRNAs and cell growth was assayed by MTT analysis. Bioinformatics prediction of the miR-429 putative target genes was performed and luciferase assays confirmed TBK1 as a direct target gene. TBK1 levels in PDAC tissues were analyzed by immunohistochemistry. Results: MiR-429 was remarkably decreased in PDAC tissues and cell lines. Lower miR-429 expression in PDAC tissues significantly correlated with shorter survival of PDAC patients. Overexpression of miR-429 inhibited PDAC cell lines growth in vitro and vice versa. TBK1 was found to be the direct target gene of miR-429. Higher TBK1 protein level in PDAC tissues correlated with shorter survival of PDAC patients. Overexpression of TBK1 partly restored cell proliferation. Conclusions: Low level of miR-429 and high level of TBK1 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-429 play its role in PDAC by targeting TBK1.

Clinical significance of serum miR-101-3p expression in patients with neonatal sepsis

2021 ◽  
Author(s):  
Juan Zhang ◽  
Xinwei Xu ◽  
Min Wang
Keyword(s):  
Neonatal Sepsis ◽  
Target Gene ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Quantitative Real Time Pcr ◽  
Tnf Α ◽  
Direct Target Gene ◽  
Direct Target ◽  
Operating Characteristic Curve

Aim: This study aimed to evaluate the levels and functions of miR-101-3p in neonatal sepsis (NS). Materials & methods: Quantitative real-time PCR was conducted to investigate the expression of miR-101-3p and the receiver operating characteristic curve was applied to manifest its diagnostic effects. Results: MiR-101-3p was increased in the NS patients and the dysregulation of miR-101-3p was associated with levels of procalcitonin, CRP, IL-8 and TNF-α. The combination of miR-101-3p and procalcitonin could function as a promising indicator in distinguishing NS patients. The silenced miR-101-3p reversed the increased levels of TNF-α and IL-8 caused by lipopolysaccharide in vitro. DUSP1 was identified as a direct target gene of miR-101-3p in NS. Conclusion: The abundance of miR-101-3p facilitated the inflammation in NS by targeting DUSP1.

scholarly journals SEMA6D, Negatively Regulated by miR-7, Contributing to Chondrocyte Catabolic and Anabolic Activities via p38 Signaling Pathway

2020 ◽  
Author(s):  
Xindie Zhou ◽  
Yi Zhang ◽  
Junjie Zhang ◽  
Zhicheng Yang ◽  
Haoyu Yang ◽  
...  
Keyword(s):  
Target Gene ◽  
Regulatory Mechanism ◽  
Regulatory Factor ◽  
Regulatory Relation ◽  
Direct Target Gene ◽  
Direct Target ◽  
Novel Therapeutic ◽  
P38 Pathway

Abstract Background: MiR-7 has been recognized as a promoting factor of osteoarthritis (OA), but the specific down-stream pathway of miR-7 still remains unknown. Further investigation of the molecular regulatory mechanism of miR-7 might help develop a novel therapeutic method for OA.Results: Here we revealed that Semaphorin 6D (SEMA6D) was a direct target gene of miR-7, of which presented a negatively regulatory relation in vitro and in vivo. Lucubration of SEMA6D suggested that SEMA6D is validated to promote the anabolic metabolism and reduce the catabolism of chondrocytes via inhibiting the activation of p38 pathway.Conclusions: Present research illustrated that SEMA6D is a negatively regulatory factor of miR-7 and a pivotal mediator of the catabolism and anabolism of chondrocytes. SEMA6D exerts its function via inhibiting the activation of p38 pathway.

scholarly journals WSB1 Regulates c-Myc Expression Through β-catenin Signaling and Forms a Feedforward Circuit Promoting the Development of Cancer

2020 ◽  
Author(s):  
Xiaomeng Gao ◽  
Yanling Gong ◽  
Jieqiong You ◽  
Meng Yuan ◽  
Haiying Zhu ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Target Gene ◽  
Regulatory Mechanism ◽  
Intervention Strategy ◽  
E3 Ubiquitin Ligase ◽  
Promoting Effect ◽  
Direct Target Gene ◽  
Direct Target

AbstractThe dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can directly transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies based on its regulatory mechanism hold great potential for cancer therapy. In this study, we found that WSB1, a direct target gene of c-Myc, can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. Luciferase-based promoter activity assays and RNA sequencing results confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and subsequently transactivated c-Myc. Of interest, the promoting effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, co-expression of WSB1 and c-Myc strongly enhanced the initiation and progression of tumours both in vitro and in vivo. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

scholarly journals Proanthocyanidins Induce miR-133b Expression to Promote Ischemic Skeletal Muscle Regeneration by Targeting MKP1

2020 ◽  
Author(s):  
Shi Chen ◽  
Chao Du ◽  
Lilong Pan ◽  
Qian Yang ◽  
Peihe Yu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Target Gene ◽  
Myogenic Differentiation ◽  
Limb Ischemia ◽  
Skeletal Muscle Regeneration ◽  
Aberrant Expression ◽  
Direct Target Gene ◽  
Direct Target

Abstract Background: Limb ischemic necrosis is mainly attributed to peripheral arterial disease (PAD). Reducing oxidative stress and promoting damaged skeletal muscle regeneration may be benefit for ischemic limb treatment. Proanthocyanidins (PC) is a powerful antioxidant and free radical scavenger, but little is known about its role and related molecular mechanism in limb ischemic injury. The current study was undertaken to explore its role in the damaged skeletal muscle regeneration both in vitro and vivo, and whether MicroRNAs (miRNAs) involved in this process. Methods: The potential effects of PC on the damaged muscle regeneration were explored in human skeletal muscle satellite cells (HSKMSCs) under hypoxic-ischemic condition and in mice limb ischemia model, then, aberrant expression of miRNAs in ischemic skeletal muscles were determined by microarray analysis, and regulatory mechanism of the specific miRNA on HSKMSCs myogenic differentiation was further investigated by gain and loss of functional experiments. Additionally, the direct target gene was examined by luciferase reporter assay.Results: In mice limb ischemia model, our results revealed that PC reduced oxidative stress level, significantly promoted ischemic limb damaged muscle regeneration and motor function recovery, then, aberrant expression of miRNAs in ischemic skeletal muscles were determined by microarray analysis, combine with the results of the RT-qPCR, the miR-133b-3p was proved to be the specific miRNA. In vitro, our results revealed that PC induced the overexpression of miR-133b to activate the p38-MAPK signal pathway and increased the myogenic differentiation-related molecules expression, which eventually promoted myotubes formation. Furthermore, MKP1 was confirmed a direct target gene of miR-133b.Conclusion: Our results suggest that PC display skeletal muscle protective properties that are mediated by miR-133b /MKP1/ p38-MAPK signal axis, offering a novel therapeutic opportunity for limb ischemic injury.

scholarly journals CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 ◽  
Vol 19 (1) ◽  
pp. 495-504 ◽  
Author(s):  
John Sok ◽  
Xiao-Zhong Wang ◽  
Nikoleta Batchvarova ◽  
Masahiko Kuroda ◽  
Heather Harding ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Target Gene ◽  
Target Genes ◽  
Direct Evidence ◽  
Nuclear Protein ◽  
Intracellular Form ◽  
Carbonic Anhydrase Vi ◽  
Responsive Element

ABSTRACT CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducibleCA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VIexpression in c/ebpβ−/− cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

scholarly journals Genome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression

2021 ◽  
Vol 9 (1) ◽  
pp. 6
Author(s):  
Narendra Pratap Singh ◽  
Bony De Kumar ◽  
Ariel Paulson ◽  
Mark E. Parrish ◽  
Carrie Scott ◽  
...  
Keyword(s):  
Dna Binding ◽  
Target Genes ◽  
Embryonic Stem ◽  
Binding Motif ◽  
Binding Assays ◽  
Histone Marks ◽  
Genome Wide ◽  
Hox Cofactors

Knowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in embryonic stem cells differentiated into neural fates. Unexpectedly, only a small number of HOXB1 bound regions (7%) correlate with binding of the known HOX cofactors PBX and MEIS. In contrast, 22% of the HOXB1 binding peaks display co-occupancy with the transcriptional repressor REST. Analyses revealed that co-binding of HOXB1 with PBX correlates with active histone marks and high levels of expression, while co-occupancy with REST correlates with repressive histone marks and repression of the target genes. Analysis of HOXB1 bound regions uncovered enrichment of a novel 15 base pair HOXB1 binding motif HB1RE (HOXB1 response element). In vitro template binding assays showed that HOXB1, PBX1, and MEIS can bind to this motif. In vivo, this motif is sufficient for direct expression of a reporter gene and over-expression of HOXB1 selectively represses this activity. Our analyses suggest that HOXB1 has evolved an association with REST in gene regulation and the novel HB1RE motif contributes to HOXB1 function in part through a repressive role in gene expression.

scholarly journals Identification ofTDRD1as a direct target gene ofERGin primary prostate cancer

2013 ◽  
Vol 133 (2) ◽  
pp. 335-345 ◽  
Author(s):  
Joost L. Boormans ◽  
Hanneke Korsten ◽  
Angelique J.C. Ziel-van der Made ◽  
Geert J.L.H. van Leenders ◽  
Carola V. de Vos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Target Gene ◽  
Primary Prostate Cancer ◽  
Direct Target Gene ◽  
Direct Target

ZNF16 (HZF1) promotes erythropoiesis and megakaryocytopoiesis via regulation of the c-KIT gene

2014 ◽  
Vol 458 (1) ◽  
pp. 171-183 ◽  
Author(s):  
Jing Chen ◽  
Xiao-Bo Li ◽  
Rui Su ◽  
Li Song ◽  
Fang Wang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Target Gene ◽  
Megakaryocytic Differentiation ◽  
Kit Gene ◽  
Direct Target Gene ◽  
Direct Target

The present study demonstrated that ZNF16 (HZF1) plays an important role in erythroid and megakaryocytic differentiation of human haematopoietic stem/progenitor cells, identified and validated c-KIT as a direct target gene of ZNF16, and demonstrated that ZNF16 functions via its regulation on the c-Kit/c-Raf/MEK/ERK/c-Jun/HEY1/GATA1 cascade.

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