scholarly journals Genomic Repeat Element Analyzer for Mammals (GREAM)

2014 ◽  
Author(s):  
Darshan S Chandrashekar ◽  
Poulami Dey ◽  
Kshitish K Acharya
Keyword(s):  
Transcriptional Regulation ◽  
Gene Expression Regulation ◽  
Mammalian Species ◽  
Query Sequence ◽  
Repeat Element ◽  
Transcription Control ◽  
Element Analysis ◽  
Repeat Elements ◽  
Specific Distribution ◽  
Genomic Repeat

Background: Understanding the mechanism behind the transcriptional regulation of genes is still a challenge. Recent findings indicate that the genomic repeat elements (such as LINES, SINES and LTRs) could play an important role in the transcription control. Hence, it is important to further explore the role of genomic repeat elements in the gene expression regulation, and perhaps in other molecular processes. Although many computational tools exists for repeat element analysis, almost all of them simply identify and/or classifying the genomic repeat elements within query sequence(s); none of them facilitate identification of repeat elements that are likely to have a functional significance, particularly in the context of transcriptional regulation. Result: We developed the 'Genomic Repeat Element Analyzer for Mammals' (GREAM) to allow gene-centric analysis of genomic repeat elements in 17 mammalian species, and validated it by comparing with some of the existing experimental data. The output provides a categorized list of the specific type of transposons, retro-transposons and other genome-wide repeat elements that are statistically over-represented across specific neighborhood regions of query genes. The position and frequency of these elements, within the specified regions, are displayed as well. The tool also offers queries for position-specific distribution of repeat elements within chromosomes. In addition, GREAM facilitates the analysis of repeat element distribution across the neighborhood of orthologous genes. Conclusion: GREAM allows researchers to short-list the potentially important repeat elements, from the genomic neighborhood of genes, for further experimental analysis. GREAM is free and available for all at http://resource.ibab.ac.in/GREAM/

scholarly journals Repeat to gene expression ratios in leukemic blast cells can stratify risk prediction in acute myeloid leukemia

2021 ◽  
Author(s):  
Megumi Onishi-Seebacher ◽  
Galina Erikson ◽  
Zoe Sawitzki ◽  
Devon Ryan ◽  
Gabriele Greve ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myeloid Leukemia ◽  
Repeat Element ◽  
Leukemic Blast ◽  
Hematopoietic Differentiation ◽  
Repeat Elements ◽  
Blast Cells ◽  
G Ratio ◽  
Patient Subgroups ◽  
Bioinformatic Approach

Abstract BackgroundRepeat elements constitute a large proportion of the human genome and recent evidence indicates that repeat element expression has functional roles in both physiological and pathological states. Specifically for cancer, transcription of endogenous retrotransposons is often suppressed in order to attenuate an anti-tumor immune response, whereas aberrant expression of heterochromatin-derived satellite RNA has been identified as a tumor driver. These insights demonstrate separate functions for the dysregulation of distinct repeat subclasses in either the attenuation or progression of human solid tumors. For hematopoietic malignancies, such as Acute Myeloid Leukemia (AML), only very few studies on the expression/dysregulation of repeat elements were done. MethodsTo study the expression of repeat elements in AML, we performed total-RNA sequencing of healthy CD34+ cells and of leukemic blast cells from primary AML patient material. We also developed an integrative bioinformatic approach that can quantify the expression of repeat transcripts from all repeat subclasses (SINE/ALU, LINE and ERV elements and satellite repeats) in relation to the expression of gene and other non-repeat transcripts. This novel approach can be used as an instructive signature (R/G ratio) for repeat element expression and has been extended to the analysis of poly(A)-RNA sequencing datasets from Blueprint and TCGA consortia that together comprise 120 AML patient samples. ResultsWe identified that repeat element expression is generally down-regulated during hematopoietic differentiation and that relative changes in repeat to gene expression (i.e. R/G ratios) can stratify risk prediction of AML patients and correlate with overall survival probabilities. A high repeat to gene expression ratio identifies AML patient subgroups with a favorable prognosis, whereas a low repeat to gene expression is prevalent in AML patient subgroups with a poor prognosis. ConclusionsWe developed an integrative bioinformatic approach that defines a general model for the analysis of repeat element dysregulation in physiological and pathological development. We find that changes in repeat to gene expression (R/G ratios) correlate with hematopoietic differentiation and can sub-stratify AML patients into low-risk and high-risk subgroups. Thus, the definition of a R/G ratio can serve as a valuable biomarker for AML and could also provide insights into differential patient response to epigenetic drug treatment.

scholarly journals Loss of the third C2H2 zinc finger of chicken KLF7 affects its transcriptional regulation activities in adipose tissue

2019 ◽  
Vol 52 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Zhiwei Zhang ◽  
Chunyan Wu ◽  
Tao Lin ◽  
Yuechan Chen
Keyword(s):  
Transcriptional Regulation ◽  
Zinc Finger ◽  
Promoter Activity ◽  
Mammalian Species ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Wild Type ◽  
C2h2 Zinc Finger ◽  
The Third ◽  
Significant Difference

Abstract KLF7, one of candidate genes in neurotherapy and metabolic syndrome, has been studied in adipogenesis of mammalian species and birds. However, the effect of the third C2H2 zinc finger of KLF7 for its transcriptional regulation in adipogenesis has not been well understood. Here, the wild-type chicken KLF7 (KLF7) overexpression plasmid, pCMV-myc-KLF7, and two plasmids of chicken KLF7 mutants, i.e. pCMV-myc-KLF7m1 with half of the third zinc finger (KLF7m1) and pCMV-myc-KLF7m2 without the third zinc finger (KLF7m2), were constructed. Luciferase reporter assay in DF1 cells showed that the effect of chicken KLF7 overexpression on the promoter activity of LPL was greater than those of KLF7m1 and KLF7m2 (P < 0.05). There was no significant difference among the overexpression of KLF7, KLF7m1 and KLF7m2 on the promoter activities of FASN, C/EBPα and FABP4 (P > 0.05). Additionally, the effects of KLF7, KLF7m1 and KLF7m2 overexpression on the promoter activity of PPARγ were different. KLF7 overexpression had no significant effect on the PPARγ promoter activity (P > 0.05), KLF7m1 overexpression suppressed PPARγ promoter activity (P < 0.05), while KLF7m2 overexpression facilitated the promoter activity of PPARγ (P < 0.05), consistent with the results of western blot analysis. Our results suggested that the third zinc finger of chicken KLF7 may play a role in its transcriptional regulation of LPL and PPARγ but has no effect on its regulation of C/EBPα, FASN and FABP4. The third zinc finger of KLF7 might be a target for the treatment of metabolic disorder in chicken.

Abstract P279: Human Angiotensin Receptor Gene Variations, Hypertension & Reno-Vascular Complications

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sudhir Jain ◽  
Natalie Sirianni ◽  
Nitin Puri ◽  
Ahmed A Khudhair ◽  
Ashok Kumar
Keyword(s):  
Blood Pressure ◽  
Transcriptional Regulation ◽  
Gene Expression Regulation ◽  
Vascular System ◽  
Receptor Gene ◽  
Vascular Complications ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Angiotensin Receptor

Angiotensin receptor type 1 (AT1R), a G-protein coupled receptor mediates the effect of angiotensin-II and contributes to the pathophysiological consequences of reno-vascular system. AT1R-signaling promotes renal sodium retention, vascular remodeling, hypertension, and end organ damage. Genetic variations that increase AT1R can cause pathological outcomes associated with renin angiotensin system overactivity. However, genetically variable, transcriptional regulation of the human AT1R gene is poorly understood. In this regard, the human AT1R gene has a haplotype block of four SNPs: T/A at -810, T/G at -713, A/C at -214, and A/G at -153 in its promoter. Variants -810T, -713T, -214A, and -153A always occur together (named haplotype-I or Hap-I) and variants -810A, -713G, -214C, and -153G always occur together (haplotype-II or Hap-II). We have found that hap-I is associated with hypertension in Caucasians. Thus, we generated transgenic (TG) mice with hap-II and I of the hAT1R gene to study its transcriptional regulation in vivo . TG mice with hap-I have higher baseline expression of hAT1R (3.9 folds) in the kidney with increased blood pressure (Hap-I, 126±3 vs. Hap II, 115±4). Since, diet-induced obesity is accompanied by systemic inflammation and redox imbalance that, in turn, alter the cellular transcriptional milieu, we gave Western diet (WD) treatment to our TG mice. Preliminary studies show that transcription factors like USF1, GR and STAT3 binds strongly (2.1; 2.3; 1.7 folds respectively Vs Hap-II) to increase hAT1R expression (5.8 folds) and resulting blood pressure (136±2 vs. 120±3 in Hap II) in TG-mice with hap-I, as compared to hap-II. Complementary experiments show increased inflammatory and redox markers in renal tissues of Hap-I mice, when compared to Hap-II, after WD; including, IL6 (5.9 fold), NOX1 (5.2 fold), CRP (9.8 fold), and TNFα (6.3 fold). Also, histochemical analysis of kidneys show an elevated pathology in Hap-I TG mice. Thus, haplotype-dependent transcriptional regulation of the hAT1R gene causes increased hAT1R expression and blood pressure, in Hap-I TG mice. Importantly, WD exacerbates this differential gene- expression regulation, further increasing hAT1R and promoting a pro-oxidant/inflammatory milieu in mice with Hap-I.

scholarly journals Squamate reptiles challenge paradigms of genomic repeat element evolution set by birds and mammals

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Giulia I. M. Pasquesi ◽  
Richard H. Adams ◽  
Daren C. Card ◽  
Drew R. Schield ◽  
Andrew B. Corbin ◽  
...  
Keyword(s):  
Repeat Element ◽  
Squamate Reptiles ◽  
Genomic Repeat ◽  
Element Evolution

scholarly journals Transcriptional regulation of PRPF31 gene expression by MSR1 repeat elements causes incomplete penetrance in retinitis pigmentosa

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Anna M. Rose ◽  
Amna Z. Shah ◽  
Giulia Venturini ◽  
Abhay Krishna ◽  
Aravinda Chakravarti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Retinitis Pigmentosa ◽  
Incomplete Penetrance ◽  
Repeat Elements

scholarly journals Transcriptional Regulation of Acyl-CoA:Glycerol-sn-3-Phosphate Acyltransferases

2019 ◽  
Vol 20 (4) ◽  
pp. 964 ◽  
Author(s):  
Ken Karasawa ◽  
Kazunari Tanigawa ◽  
Ayako Harada ◽  
Atsushi Yamashita
Keyword(s):  
Transcriptional Regulation ◽  
Mrna Expression ◽  
Regulatory Element ◽  
Mammalian Species ◽  
Mitochondrial Outer Membrane ◽  
Endoplasmic Reticulum Membrane ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Element ◽  
Key Enzyme

Acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT) is an enzyme responsible for the rate-limiting step in the synthesis of glycerophospholipids and triacylglycerol (TAG). The enzymes of mammalian species are classified into four isoforms; GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, whereas GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane. The activity of each enzyme expressed is associated with physiological and pathological functions. The transcriptional regulation is well known, particularly in GPAT1. GPAT1 mRNA expression is mainly regulated by the binding of the transcriptional factor SREBP-1c to the specific element (the sterol regulatory element) flanking the GPAT1 promoter. The TAG level is controlled by the insulin-induced transcriptional expression of GPAT1, which occupies most of the GPAT activity in the liver. The transcriptional regulation of the other three GPAT isoforms remains undetermined in detail. It is predicted that retinoic acid serves as a transcription factor in the GPAT2 promoter. PPARγ (peroxisome proliferator-activated receptor γ) increases the mRNA expression of GPAT3, which is associated with TAG synthesis in adipose tissues. Although GPAT has been considered to be a key enzyme in the production of TAG, unexpected functions have recently been reported, particularly in GPAT2. It is likely that GPAT2 is associated with tumorigenesis and normal spermatogenesis. In this review, the physiological and pathophysiological roles of the four GPAT isoforms are described, alongside the transcriptional regulation of these enzymes.

Post-transcriptional regulation of gene expression by alternative 5′-untranslated regions in carcinogenesis

2008 ◽  
Vol 36 (4) ◽  
pp. 708-711 ◽  
Author(s):  
Laura Smith
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Cancer Biology ◽  
Regulation Of Gene Expression ◽  
Untranslated Regions ◽  
Specific Distribution ◽  
Eukaryotic Gene ◽  
Multiple Alternative ◽  
Post Transcriptional Regulation ◽  
Inappropriate Expression

Post-transcriptional regulation, via 5′-UTRs (5′-untranslated regions), plays an important role in the control of eukaryotic gene expression. Recent analyses of the mammalian transcriptome suggest that most of the genes express multiple alternative 5′-UTRs and inappropriate expression of these regions has been shown to contribute to the development of carcinogenesis. The present review will focus on the complex post-transcriptional regulation of ERβ (oestrogen receptor β) expression. In particular, results from our laboratory suggest that the expression of alternative 5′-UTRs plays a key role in determining the level of ERβ protein expression. We have also shown that these alternative ERβ 5′-UTRs have a tissue-specific distribution and are differentially expressed between various normal and tumour tissues. Our results also suggest that alternative 5′-UTRs can influence downstream splicing events, thereby perhaps affecting ERβ function. These results suggest that alternative 5′-UTRs may have an overall influence on ER activity and this may have important implications for our understanding of cancer biology and treatment.

scholarly journals Transposable element insertions shape gene regulation and melanin production in a fungal pathogen

2018 ◽  
Author(s):  
Parvathy Krishnan ◽  
Lukas Meile ◽  
Clémence Plissonneau ◽  
Xin Ma ◽  
Fanny E. Hartmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transposable Elements ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Gene Expression Regulation ◽  
Phenotypic Diversity ◽  
Positive Contribution ◽  
Zymoseptoria Tritici ◽  
Melanin Production

AbstractBackgroundVariation in gene expression contributes to phenotypic diversity within species and adaptation. However, very few cases of adaptive regulatory changes have been reported and the mechanisms underlying variation in gene expression remain largely unexplored. Fungal pathogen genomes are highly plastic and harbour numerous insertions of transposable elements, which can potentially contribute to gene expression regulation. In this work we elucidated how transposable elements contribute to variation of melanin accumulation, a quantitative adaptive trait of fungal pathogens that is involved in survival under stress conditions.ResultsWe demonstrated that differential transcriptional regulation of the gene encoding the transcription factor Zmr1, which controls expression of the genes in the melanin biosynthetic gene cluster, is responsible for variation in melanin accumulation in the fungal plant pathogenZymoseptoria tritici. We show that differences in melanin levels between two strains ofZ. triticiare due to two levels of transcriptional regulation: 1) variation in the promoter sequence ofZmr1, and 2) an insertion of transposable elements upstream of theZmr1promoter. Remarkably, independent insertions of transposable elements upstream ofZmr1occurred in 9% ofZ. triticistrains from around the world and negatively regulatedZmr1expression, contributing to melanin accumulation variation.ConclusionsOur studies demonstrate that different layers of transcriptional control fine-tune the synthesis of melanin. These regulatory mechanisms potentially evolved to balance the fitness costs associated with melanin production against its positive contribution to survival in stressful environments.

Involving repetitive regions in scaffolding improvement

2021 ◽  
Author(s):  
Quentin Delorme ◽  
Rémy Costa ◽  
Yasmine Mansour ◽  
Anna-Sophie Fiston-Lavier ◽  
Annie Chateau
Keyword(s):  
Transposable Element ◽  
Repeat Element ◽  
Assembly Process ◽  
Repeat Elements ◽  
Before And After ◽  
Genome Assemblies

In this paper, we investigate througth a premilinary study the influence of repeat elements during the assembly process. We analyze the link between the presence and the nature of one type of repeat element, called transposable element (TE) and misassembly events in genome assemblies. We propose to improve assemblies by taking into account the presence of repeat elements, including TEs, during the scaffolding step. We analyze the results and relate the misassemblies to TEs before and after correction.

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