scholarly journals Unravel the Mystery of NIC1-locus on Nicotine Biosynthesis Regulation in Tobacco

2020 ◽  
Author(s):  
Xueyi Sui ◽  
He Xie ◽  
Zhijun Tong ◽  
Hongbo Zhang ◽  
Zhongbang Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Cluster ◽  
Bulked Segregant Analysis ◽  
Ectopic Expression ◽  
Ethylene Response Factor ◽  
Gene Promoters ◽  
Gene Expressions ◽  
Linkage Marker ◽  
Nicotine Biosynthesis ◽  
Ja Signaling

ABSTRACTBackgroundNicotine biosynthesis is mainly regulated by jasmonate (JA) signaling cascade in Nicotiana tabacum. As an allotetraploid species, the regulation of nicotine biosynthesis has been genetically verified via two unlinked NIC loci (named as NIC1 and NIC2) which are possibly originated from its two ancestral diploids. Previously, a N. tomentosiformis originated ethylene response factor (ERF) gene cluster was identified as the NIC2-locus which has been demonstrated positively regulates nicotine accumulation in N. tabacum.ResultsHere, we describe the genetic mapping of NIC1-locus, the major nicotine regulatory locus, by using a NIC1-locus segregating population through bulked segregant analysis. We identified two linkage marker TM23004 and TM22038 were delimited the NIC1-locus within a ~34.3-Mb genomic region at pseudochromosome 07 of tobacco genome. Genomic scan within this region revealed a NIC2-like locus ERF gene cluster exist in. To verify this ERF gene cluster is the genetically called “NIC1-locus”, different functional experiments based on most of the ERFs in regulating nicotine biosynthesis and their influences on alkaloid accumulations have been carried out. Collinearity analysis showed that NIC1-locus ERF genes are originated from N. sylvestris and exclusively expressed in root tissues. In addition, transcriptomic results indicate that NIC1-locus ERF genes are coexpressed with the NIC2-locus ERF genes and other nicotine biosynthetic genes and regulators after JA induction. Furthermore, the suppressed expression of four ERFs of the NIC1-locus genes corresponding with decreased NtPMT and NtQPT expression in NtMYC2-RNAi lines indicates the selected NIC1-locus ERFs function in downstream of NtMYC2 in the JA signaling cascades. In the meanwhile, the alkaloid levels are also determined by the amplitude of the four ERF gene expressions in both wild type and LA mutant. Additionally, in vitro binding assays, transient activation assays, and ectopic expression in transgenic plants demonstrate that these ERF genes are able to bind the GCC-box elements residing in the step-limiting gene promoters (such as NtPMT2, NtQPT2) and functional redundant but quantitatively transactivate nicotine biosynthetic gene expression. For nic1-locus mutation, two different sizes of deletions (nic1-S and nic1-B) were identified which occurred at the surrounding regions of the NIC1-locus gene cluster, which might disrupt, to some extent, chromosomal microenvironment and change gene expression around the deletion regions (including NIC1-locus ERFs), resulting in the decreased expression levels of NIC1-locus ERFs (such as NtERF199) and reduced alkaloid accumulation in the nic1-locus mutant.ConclusionsOur findings not only provide insight in to the mechanism of the NIC1-locus ERFs in the regulatory network of nicotine biosynthesis, but also unraveled the theoretical basis of the nic1-locus mutation in low nicotine mutant. These functional verified NIC1-locus ERF genes can be further used as potential target(s) for ethyl methanesulfonate-based mutagenesis to manipulate nicotine level in tobacco variety in tobacco breeding program.

Inclusion of HOXA Genes in Genetic and Biological Networks Defining Human Acute T-Cell Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1110-1110
Author(s):  
Jean Soulier ◽  
Emmanuelle Clappier ◽  
Jean-Michel Cayuela ◽  
Armelle Regnault ◽  
Marina Garcia-Peydro ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Gene Cluster ◽  
Expression Analysis ◽  
Large Scale ◽  
Lymphoblastic Leukemia ◽  
Ectopic Expression ◽  
Molecular Networks ◽  
Human T Cell ◽  
Hoxa Genes

Abstract We have identified a new recurrent chromosomal translocation, targeting the major homeobox gene cluster HOXA in human T-cell acute lymphoblastic leukemia (T-ALL). Four cases were characterized using a combination of FISH, Southern blot, breakpoint region sequencing, and a large scale expression analysis of a series of T-ALL. Specific RQ-PCR analysis of the HOXA1 to HOXA13 transcripts showed that the whole HOXA gene cluster expression was dramatically deregulated in the HOXA-rearranged cases, and also in the MLL and CALM-AF10-related T-ALL, strongly suggesting that HOXA genes are oncogenic in these types of leukemia. The HOXA-rearranged cases were included in a general portrait of T-ALL based on large scale expression analysis, showing that a new homogeneous T-ALL subgroup is defined by this chromosomal rearrangement. Moreover, patterns of gene expression associated to the distinct T-ALL oncogenic subgroups were compared with gene expression in normal human thymic sub-populations (11 purified sub-populations). Inappropriate use or perturbation of some specific molecular networks involved in thymic differentiation could be detected in the T-ALL cells. Also, we found that abnormal, frequently ectopic, expression of at least one developmental gene, including HOXA, TLX1/HOX11, TLX3/HOX11L2 and a few more, could be identified in most of the T-ALL cases. Our data strongly support the view that the abnormal expression of developmental genes, including the prototypical major homeobox genes HOXA in some cases, is critical in T-ALL oncogenesis.

Ectopic Expression of HDAC9 in Murine Lymphoid System Leads to Altered Lymphocyte Numbers and Proliferation as Well as Predisposition to Tumorigenesis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 376-376
Author(s):  
Veronica S. Gil ◽  
Louise M.C. Howell ◽  
Jenny Yeung ◽  
Kevin R. Petrie ◽  
Adrian Smith ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Ectopic Expression ◽  
Cell Development ◽  
B Cell Development ◽  
Gene Promoters ◽  
Marginal Zone B Cells ◽  
Lymphoid System

Abstract Reversible acetylation of lysine residues on histone tails is associated with changes to chromatin structure and plays a key role in regulation of gene expression. In this process, histone hypoacetylation is generally associated with gene silencing and pharmacological inhibition of histone deacetylases (HDACs) leads usually to activation of gene expression. Decreased histone acetylation is a hallmark of cancer cells and increased HDAC expression or their mistargetting to specific gene promoters has been associated with a variety of tumors. In the past we have identified and cloned class IIa HDAC9. The HDAC9 gene is located in chromosome 7p21, which is frequently amplified in B-cell tumours such as mantle cell lymphoma (MCL) and in B-cell non-Hodgkin’s lymphoma cell lines. Consistently, initial analysis of patient samples and/or publicly available microarray data highlighted high levels of HDAC9 expression in chronic lymphocytic leukemia, folicullar lymphoma and MCL. Within the normal lymphoid system, HDAC9 is co-expressed with BCL-6 in germinal center B-cells (∼60% of cells). HDAC9 is also expressed in marginal zone B cells and a fraction of CD38 or CD27 positive subepithelial tonsilar cells. In order to examine the role of HDAC9 in the lymphoid development and pathogenesis of lymphoid malignancies we used Ig heavy chain enhancer (Eμ), which drives gene expression from early stages of B-cell development, to ectopically express HDAC9 in transgenic mice. Hemizygous and homozygous mice expressing Flag epitope tagged human HDAC9 (fHDAC9) transgene display throughout their lifespan altered B-cell development. Immunophenotypic analysis of B-cells isolated from bone marrow (BM) revealed an absence of cells expressing the pre-B/immature-B cell markers normally associated with C-E Hardy’s fractions. In vitro functional clonogenic assays for IL-7 responsive BM-derived B-cell progenitors demonstrated an increase (∼50%) in colony numbers in the transgenic BM. Moreover, morphologic and flow cytometric analyses of the transgenic colonies, but not those derived from normal BM, revealed the presence of granulocyte/macrophage colony forming units expressing the HDAC9 transgene, suggesting a lympho-myeloid lineage switch. This correlates with the finding that extramedullary myelopoiesis occurs in a fraction of mice presenting splenomegaly (44%). Furthermore, a subgroup of homozygous Eμ-fHDAC9 mice (n=16) developed tumours (81%) at middle age, and present with enlarged lymph nodes (6%) and abnormal hematopoietic elements in peripheral blood and BM. Taken together these data suggest that HDAC9 plays a role in B-cell maturation and its ectopic expression in early B-cells leads to perturbation of normal B-cell development, possibly predisposing transgenic mice to tumorigenesis.

scholarly journals Dual-located WHIRLY1 affects salicylic acid homeostasis via coordination of ICS1, PAL1 and BSMT1 during Arabidopsis plant aging

2020 ◽  
Author(s):  
Wenfang Lin ◽  
Hong Zhang ◽  
Dongmei Huang ◽  
Dirk Schenke ◽  
Daguang Cai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salicylic Acid ◽  
Early Stage ◽  
Ectopic Expression ◽  
Transcriptional Analysis ◽  
Ethylene Response Factor ◽  
Loss Of Function ◽  
Developmental Gene Expression ◽  
Stage Of Development ◽  
R2r3 Myb

AbstractSalicylic acid (SA) homeostasis determines also developmental senescence and is spatiotemporally controlled by various mechanisms, including biosynthesis, transport and conjugate formation. The alteration of WHIRLY1 (WHY1), a repressor of leaf natural senescence, with respect to allocation in the nucleus or chloroplast causes a perturbation in SA homeostasis, resulting in adverse plant senescence phenotypes. Loss of WHY1 resulted in a 5 days earlier SA peak compared to wild type plants which accumulated SA at 42 days after germination. SA accumulation coincided with an early leaf senescence phenotype, which could be prevented by ectopic expression of the nuclear WHY1 isoform (nWHY1). However, expressing the plastid WHY1 isoform (pWHY1) greatly enhanced cellular SA levels. A global transcriptional analysis in WHY1 loss-of-function background by expressing either pWHY1 or nWHY1 indicated that hormone metabolism related genes were most significantly altered. The pWHY1 isoform predominantly affected stress related gene expression, while the nWHY1 controlled rather developmental gene expression. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) assays indicated that nWHY1 directly binds to the promoter region of isochorismate synthase (ICS1) to activate its expression at later stage, but indirectly activated S-adenosyl-L-methionine-dependent methyltransferase (BSMT1) gene expression via ethylene response factor 109 (ERF109), while repressing phenylalanine ammonia lyase (PAL1) expression via R2R3-MYB member 15 (MYB15) at the early stage of development. Interestingly, rising SA levels exerted a feedback effect by inducing nWHY1 modification and pWHY1 accumulation. Thus, the alteration of WHY1 organelle isoforms and the feedback of SA intervened in a circularly integrated regulatory network during developmental or stress-induced senescence in Arabidopsis.

Chemoprotective Effects of Propolis on Aflatoxin B1-Induced Hepatotoxicity in Rats: Oxidative Damage and Hepatotoxicity by Modulating TP53, Oxidative Stress

2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Oxidative Damage ◽  
Aflatoxin B1 ◽  
Tp53 Gene ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Gene Expressions ◽  
Cat Gene ◽  
Gst Activity

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.

scholarly journals Transcriptional enhancers and their communication with gene promoters

2021 ◽  
Author(s):  
Helen Ray-Jones ◽  
Mikhail Spivakov
Keyword(s):  
Gene Expression ◽  
Functional Genomics ◽  
Target Genes ◽  
Gene Control ◽  
Gene Promoters ◽  
Joint Effects ◽  
Transcriptional Enhancers ◽  
Quantitative Understanding ◽  
The Right ◽  
The Way

AbstractTranscriptional enhancers play a key role in the initiation and maintenance of gene expression programmes, particularly in metazoa. How these elements control their target genes in the right place and time is one of the most pertinent questions in functional genomics, with wide implications for most areas of biology. Here, we synthesise classic and recent evidence on the regulatory logic of enhancers, including the principles of enhancer organisation, factors that facilitate and delimit enhancer–promoter communication, and the joint effects of multiple enhancers. We show how modern approaches building on classic insights have begun to unravel the complexity of enhancer–promoter relationships, paving the way towards a quantitative understanding of gene control.

scholarly journals Mining The Cancer Genome Atlas gene expression data for lineage markers in distinguishing bladder urothelial carcinoma and prostate adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ewe Seng Ch’ng
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
The Cancer Genome Atlas ◽  
Relative Importance ◽  
Expression Data ◽  
Gene Expressions ◽  
Urothelial Carcinomas ◽  
Cancer Genome Atlas ◽  
Lineage Markers ◽  
Genome Atlas

AbstractDistinguishing bladder urothelial carcinomas from prostate adenocarcinomas for poorly differentiated carcinomas derived from the bladder neck entails the use of a panel of lineage markers to help make this distinction. Publicly available The Cancer Genome Atlas (TCGA) gene expression data provides an avenue to examine utilities of these markers. This study aimed to verify expressions of urothelial and prostate lineage markers in the respective carcinomas and to seek the relative importance of these markers in making this distinction. Gene expressions of these markers were downloaded from TCGA Pan-Cancer database for bladder and prostate carcinomas. Differential gene expressions of these markers were analyzed. Standard linear discriminant analyses were applied to establish the relative importance of these markers in lineage determination and to construct the model best in making the distinction. This study shows that all urothelial lineage genes except for the gene for uroplakin III were significantly expressed in bladder urothelial carcinomas (p < 0.001). In descending order of importance to distinguish from prostate adenocarcinomas, genes for uroplakin II, S100P, GATA3 and thrombomodulin had high discriminant loadings (> 0.3). All prostate lineage genes were significantly expressed in prostate adenocarcinomas(p < 0.001). In descending order of importance to distinguish from bladder urothelial carcinomas, genes for NKX3.1, prostate specific antigen (PSA), prostate-specific acid phosphatase, prostein, and prostate-specific membrane antigen had high discriminant loadings (> 0.3). Combination of gene expressions for uroplakin II, S100P, NKX3.1 and PSA approached 100% accuracy in tumor classification both in the training and validation sets. Mining gene expression data, a combination of four lineage markers helps distinguish between bladder urothelial carcinomas and prostate adenocarcinomas.

scholarly journals The crest phenotype in domestic chicken is caused by a 197 bp duplication in the intron of HOXC10

2021 ◽  
Author(s):  
Jingyi Li ◽  
Mi-Ok Lee ◽  
Brian W Davis ◽  
Ping Wu ◽  
Shu-Man Hsieh-Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Genome Sequencing ◽  
Diagnostic Test ◽  
Genome Sequencing ◽  
Ectopic Expression ◽  
Body Region ◽  
Whole Genome ◽  
Dorsal Skin ◽  
Conserved Sequence ◽  
Evolutionarily Conserved

Abstract The Crest mutation in chicken shows incomplete dominance and causes a spectacular phenotype in which the small feathers normally present on the head are replaced by much larger feathers normally present only in dorsal skin. Using whole genome sequencing, we show that the crest phenotype is caused by a 197 bp duplication of an evolutionarily conserved sequence located in the intron of HOXC10 on chromosome 33. A diagnostic test showed that the duplication was present in all 54 crested chickens representing eight breeds and absent from all 433 non-crested chickens representing 214 populations. The mutation causes ectopic expression of at least five closely linked HOXC genes, including HOXC10, in cranial skin of crested chickens. The result is consistent with the interpretation that the crest feathers are caused by an altered body region identity. The upregulated HOXC gene expression is expanded to skull tissue of Polish chickens showing a large crest often associated with cerebral hernia, but not in Silkie chickens characterized by a small crest, both homozygous for the duplication. Thus, the 197 bp duplication is required for the development of a large crest and susceptibility to cerebral hernia because only crested chicken show this malformation. However, this mutation is not sufficient to cause herniation because this malformation is not present in breeds with a small crest, like Silkie chickens.

scholarly journals Histochemical Characterisation and Gene Expression Analysis of Skeletal Muscles from Maremmana and Aubrac Steers Reared on Grazing and Feedlot Systems

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 656
Author(s):  
Giulia Foggi ◽  
Francesca Ciucci ◽  
Maria Conte ◽  
Laura Casarosa ◽  
Andrea Serra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Muscle Fibre ◽  
Skeletal Muscles ◽  
Gene Expression Analysis ◽  
Type I ◽  
Triceps Brachii ◽  
Gene Expressions ◽  
Muscle Properties ◽  
Voluntary Physical Activity

This study aimed to characterise the fibre composition of Triceps brachii (TB) and Semimembranosus (SM) muscles from 20 Maremmana (MA) and 20 Aubrac (AU) steers, and the effect of grazing activity in comparison with feedlot system. The histochemical method was performed with the m-ATPase method with an acid pre-incubation, thus allowing to distinguish type I, IIA, and IIB fibres. Additionally, on total RNA extracted from SM muscle, the expressions of atp1a1, mt-atp6, and capn1 genes were evaluated, in order to find potential associations with muscle fibre histochemical characteristics. In SM muscle, the MA steers had the greater frequency of oxidative fibres (type I and IIA) and the higher atp1a1 expression, in comparison to AU steers. Conversely, AU steers had a greater frequency of type IIB fibres, and the higher capn1 expression. A similar histochemical pattern was observed in TB muscle. The grazing activity was probably insufficient to determine differences both for fibre proportion and size, and gene expressions, except for mt-atp6 expression that was surprisingly highest in feedlot MA in comparison to other steers. These findings further the knowledge of muscle properties belonging to these breeds, and the effect of voluntary physical activity since few studies were available in this regard.

scholarly journals Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Fatemeh Khodabandehloo ◽  
Sara Taleahmad ◽  
Reza Aflatoonian ◽  
Farzad Rajaei ◽  
Zahra Zandieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Hub Genes ◽  
Gene Expressions ◽  
Cell Based Therapy ◽  
Wnt Pathways ◽  
Key Pathways

Abstract Background Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

scholarly journals Hesx1 homeodomain protein represses transcription as a monomer and antagonises transactivation of specific sites as a homodimer

2002 ◽  
Vol 28 (3) ◽  
pp. 193-205 ◽  
Author(s):  
J Quirk ◽  
P Brown
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Binding Site ◽  
Anterior Pituitary ◽  
Homeodomain Protein ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Differentiation Markers ◽  
Proximal Half ◽  
Dna Binding Site

The homeobox repressor Hesx1, expressed throughout Rathke's pouch and required for normal pituitary development, has been implicated in anterior pituitary pathogenesis in man. Prolonged expression of Hesx1 delays the appearance of anterior pituitary terminal differentiation markers in mice, particularly the gonadotroph hormones. We tested if Hesx1 could modulate gonadotrophin gene expression directly, and found that Hesx1 repressed both common alpha subunit (alpha GSU) and luteinising hormone beta-subunit (LH beta) gene promoters. Repression mapped to the Pitx1 homeodomain protein transactivation site in the proximal alpha GSU promoter, but did not map to the equivalent site on LH beta. Hesx1 repression of the alpha GSU Pitx1 site was overridden by co-transfection of Pitx1. In contrast, Hesx1 antagonised Pitx1 transactivation of LH beta in a dose-dependent manner. This was due to monomeric binding of Hesx1 on alpha GSU and homodimerisation on LH beta. The homodimerisation site comprises the Pitx1 DNA binding site and a proximal binding site, and mutation of either inhibited homodimer formation. Conversion of the LH beta Pitx1 DNA binding site to an alpha GSU-type did not promote homodimer formation, arguing that Hesx1 has pronounced site selectivity. Furthermore, mutation of the proximal half of the homodimerisation site blocked Hesx1 antagonisation of Pitx1 transactivation. We conclude that Hesx1 monomers repress gene expression, and homodimers block specific transactivation sites.

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