scholarly journals Cap analysis of gene expression (CAGE) sequencing reveals alternative promoter usage in complex disease

2021 ◽  
Author(s):  
Sonal Dahale ◽  
Jorge Ruiz-Orera ◽  
Jan Silhavy ◽  
Norbert Hubner ◽  
Sebastiaan van Heesch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Disease ◽  
Complex Diseases ◽  
Alternative Promoter ◽  
Brown Norway ◽  
Specific Gene ◽  
Insulin Receptor Gene ◽  
Promoter Usage ◽  
Cap Analysis

The role of alternative promoter usage in tissue specific gene expression has been well established, however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) tag sequencing from the left ventricle (LV) of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, the Brown Norway (BN) to understand role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites (TSS) in the rat LV, including 1,970 novel cardiac TSS resulting in new transcripts. We identified 27 genes with alternative promoter usage between SHR and BN which could lead to protein isoforms differing at the amino terminus between two strains. Additionally, we identified 475 promoter switching events where a shift in TSS usage was within 100bp between SHR and BN, altering length of the 5 prime UTR. Genomic variants located in the shifting promoter regions showed significant allelic imbalance in F1 crosses, confirming promoter shift. We found that the insulin receptor gene (Insr) showed a switch in promoter usage between SHR and BN in heart and liver. The Insr promoter shift was significantly associated with insulin levels and blood pressure within a panel of BXH/HXB recombinant inbred (RI) rat strains. This suggests that the hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

scholarly journals Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension

2022 ◽  
Vol 5 (4) ◽  
pp. e202101234
Author(s):  
Sonal Dahale ◽  
Jorge Ruiz-Orera ◽  
Jan Silhavy ◽  
Norbert Hübner ◽  
Sebastiaan van Heesch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Rat Model ◽  
Alternative Promoter ◽  
Brown Norway ◽  
Transcription Start ◽  
Transcription Start Sites ◽  
Promoter Usage ◽  
Cap Analysis

The role of alternative promoter usage in tissue-specific gene expression has been well established; however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) sequencing from the left ventricle of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, Brown Norway to understand the role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites in the rat left ventricle, including 1,970 novel cardiac transcription start sites. We identified 28 genes with alternative promoter usage between SHR and Brown Norway, which could lead to protein isoforms differing at the amino terminus between two strains and 475 promoter switching events altering the length of the 5′ UTR. We found that the shift in Insr promoter usage was significantly associated with insulin levels and blood pressure within a panel of HXB/BXH recombinant inbred rat strains, suggesting that hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

scholarly journals Altered Enhancer and Promoter Usage Leads to Differential Gene Expression in the Normal and Failed Human Heart

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Anthony M. Gacita ◽  
Lisa Dellefave-Castillo ◽  
Patrick G.T. Page ◽  
David Y. Barefield ◽  
J. Andrew Wasserstrom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Regulatory Function ◽  
Specific Gene ◽  
Data Set ◽  
Promoter Usage ◽  
Additional Support ◽  
Cap Analysis ◽  
Genetic Contributions

Background: The failing heart is characterized by changes in gene expression. However, the regulatory regions of the genome that drive these gene expression changes have not been well defined in human hearts. Methods: To define genome-wide enhancer and promoter use in heart failure, cap analysis of gene expression sequencing was applied to 3 healthy and 4 failed human hearts to identify promoter and enhancer regions used in left ventricles. Healthy hearts were derived from donors unused for transplantation and failed hearts were obtained as discarded tissue after transplantation. Results: Cap analysis of gene expression sequencing identified a combined potential for ≈23 000 promoters and ≈5000 enhancers active in human left ventricles. Of these, 17 000 promoters and 1800 enhancers had additional support for their regulatory function. Comparing promoter usage between healthy and failed hearts highlighted promoter shifts which altered aminoterminal protein sequences. Enhancer usage between healthy and failed hearts identified a majority of differentially used heart failure enhancers were intronic and primarily localized within the first intron, revealing this position as a common feature associated with tissue-specific gene expression changes in the heart. Conclusions: This data set defines the dynamic genomic regulatory landscape underlying heart failure and serves as an important resource for understanding genetic contributions to cardiac dysfunction. Additionally, regulatory changes contributing to heart failure are attractive therapeutic targets for controlling ventricular remodeling and clinical progression.

scholarly journals Enhancer and promoter usage in the normal and failed human heart

2020 ◽  
Author(s):  
Anthony M. Gacita ◽  
Lisa Dellefave-Castillo ◽  
Patrick G. T. Page ◽  
David Y. Barefield ◽  
J. Andrew Waserstrom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Specific Gene ◽  
Amino Terminal ◽  
Short Rnas ◽  
First Intron ◽  
Promoter Usage ◽  
Cap Analysis ◽  
Genetic Contributions ◽  
Regulatory Landscape

ABSTRACTThe failed heart is characterized by re-expression of a fetal gene program, which contributes to adaptation and maladaptation in heart failure. To define genomewide enhancer and promoter use in heart failure, Cap Analysis of Gene Expression (CAGE-seq) was applied to healthy and failed human left ventricles to define short RNAs associated with both promoters and enhancers. Integration of CAGE-seq data with RNA sequencing identified a combined ∼17,000 promoters and ∼1,500 enhancers active in healthy and failed human left ventricles. Comparing promoter usage between healthy and failed hearts highlighted promoter shifts which altered amino-terminal protein sequences. Comparing enhancer usage between healthy and failed hearts revealed a majority of differentially utilized heart failure enhancers were intronic and primarily localized within the first intron, identifying this position as a common feature associated with tissue-specific gene expression changes in the heart. This dataset defines the dynamic genomic regulatory landscape underlying heart failure and serves as an important resource for understanding genetic contributions to cardiac dysfunction.

scholarly journals Role of cyclic AMP in the control of cell-specific gene expression

1993 ◽  
Vol 4 (6) ◽  
pp. 204-209 ◽  
Author(s):  
Wolfgang Schmid ◽  
Doris Nitsch ◽  
Michael Boshart ◽  
Günther Schütz
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Specific Gene ◽  
Specific Gene Expression

scholarly journals Oestrogen receptors and antioestrogen treatment of hormone-dependent tumours

2018 ◽  
Vol 49 (2) ◽  
pp. 91
Author(s):  
N. G. KOSTOMITSOPOULOS (Ν.Γ. ΚΩΣΤΟΜΗΤΣΟΠΟΥΛΟΣ)
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Sequences ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Specific Gene ◽  
Oestrogen Receptors ◽  
Human Breast ◽  
Potential Use

The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences. The study of the role of oestrogen receptor on the expression of the mitogenic actionof oestrogens and oncogenesis lead biomedical research in new approaches of the treatment of oestrogen-dependent tumors by using antioestrogens. Main mechanism of action of antioestrogens is the prevention of oestrogen action by blocking the binding of oestradiol to the oestrogen receptor. Tamoxifen, the most wellknown antioestrogen, is widely used as adjuvant therapy in all stages of human breast cancer. Recently interest is focused on the potential use of "pure" antioestrogens. The use of antioestrogens in veterinary oncology is also under discussion.

scholarly journals Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies

Blood ◽  
2019 ◽  
Vol 134 (24) ◽  
pp. 2195-2208 ◽  
Author(s):  
Daniel Sasca ◽  
Haiyang Yun ◽  
George Giotopoulos ◽  
Jakub Szybinski ◽  
Theo Evan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Potential Role ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Myeloid Malignancy ◽  
Erythroid Maturation ◽  
Acute Myeloid

Cohesin mutations are common in myeloid malignancy. Sasca et al elucidate the potential role of cohesin loss in myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). They demonstrate that cohesin binding is critical for erythroid-specific gene expression and that reduction in cohesin impairs terminal erythroid maturation and promotes myeloid malignancy.

scholarly journals Disease Ionomics: Understanding the Role of Ions in Complex Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8646
Author(s):  
Yan Zhang ◽  
Yinzhen Xu ◽  
Lin Zheng
Keyword(s):  
Complex Disease ◽  
Dynamic Network ◽  
Complex Diseases ◽  
Living Organism ◽  
Future Trends ◽  
Pathological Conditions ◽  
Systematic Understanding ◽  
Elemental Profiling ◽  
Made In

Ionomics is a novel multidisciplinary field that uses advanced techniques to investigate the composition and distribution of all minerals and trace elements in a living organism and their variations under diverse physiological and pathological conditions. It involves both high-throughput elemental profiling technologies and bioinformatic methods, providing opportunities to study the molecular mechanism underlying the metabolism, homeostasis, and cross-talk of these elements. While much effort has been made in exploring the ionomic traits relating to plant physiology and nutrition, the use of ionomics in the research of serious diseases is still in progress. In recent years, a number of ionomic studies have been carried out for a variety of complex diseases, which offer theoretical and practical insights into the etiology, early diagnosis, prognosis, and therapy of them. This review aims to give an overview of recent applications of ionomics in the study of complex diseases and discuss the latest advances and future trends in this area. Overall, disease ionomics may provide substantial information for systematic understanding of the properties of the elements and the dynamic network of elements involved in the onset and development of diseases.

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