Alternative promoter usage generates multiple evolutionarily conserved isoforms ofDrosophila DOA kinase

genesis ◽  
2008 ◽  
Vol 46 (3) ◽  
pp. 132-143 ◽  
Author(s):  
Arlette Kpebe ◽  
Leonard Rabinow
Keyword(s):  
Alternative Promoter ◽  
Evolutionarily Conserved ◽  
Promoter Usage

scholarly journals Two biochemically distinct and tissue-specific twinfilin isoforms are generated from the mouse Twf2 gene by alternative promoter usage

2008 ◽  
Vol 417 (2) ◽  
pp. 593-600 ◽  
Author(s):  
Elisa M. Nevalainen ◽  
Aneta Skwarek-Maruszewska ◽  
Attila Braun ◽  
Markus Moser ◽  
Pekka Lappalainen
Keyword(s):  
Actin Filament ◽  
Alternative Promoter ◽  
Actin Dynamics ◽  
Tissue Specific ◽  
Capping Protein ◽  
Muscle Tissues ◽  
Evolutionarily Conserved ◽  
Cytoskeletal Dynamics ◽  
Promoter Usage ◽  
End Capping

Twf (twinfilin) is an evolutionarily conserved regulator of actin dynamics composed of two ADF-H (actin-depolymerizing factor homology) domains. Twf binds actin monomers and heterodimeric capping protein with high affinity. Previous studies have demonstrated that mammals express two Twf isoforms, Twf1 and Twf2, of which at least Twf1 also regulates cytoskeletal dynamics by capping actin filament barbed-ends. In the present study, we show that alternative promoter usage of the mouse Twf2 gene generates two isoforms, which differ from each other only at their very N-terminal region. Of these isoforms, Twf2a is predominantly expressed in non-muscle tissues, whereas expression of Twf2b is restricted to heart and skeletal muscle. Both proteins bind actin monomers and capping protein, as well as efficiently capping actin filament barbed-ends. However, the N-terminal ADF-H domain of Twf2b interacts with ADP-G-actin with a 5-fold higher affinity than with ATP-G-actin, whereas the corresponding domain of Twf2a binds ADP-G-actin and ATP-G-actin with equal affinities. Taken together, these results show that, like Twf1, mouse Twf2 is a filament barbed-end capping protein, and that two tissue-specific and biochemically distinct isoforms are generated from the Twf2 gene through alternative promoter usage.

scholarly journals Widespread overexpression from the four DNA hypermethylated HOX clusters in aggressive ( IDH wt) glioma is associated with H3K27me3 depletion and alternative promoter usage

2021 ◽  
Author(s):  
Elisa Le Boiteux ◽  
Franck Court ◽  
Pierre‐Olivier Guichet ◽  
Catherine Vaurs‐Barrière ◽  
Isabelle Vaillant ◽  
...  
Keyword(s):  
Alternative Promoter ◽  
Promoter Usage ◽  
Hox Clusters

scholarly journals Whole-transcriptome splicing profiling of E7.5 mouse primary germ layers reveals frequent alternative promoter usage during mouse early embryogenesis

Biology Open ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. bio032508 ◽  
Author(s):  
Xukun Lu ◽  
Zhen-Ao Zhao ◽  
Xiaoqing Wang ◽  
Xiaoxin Zhang ◽  
Yanhua Zhai ◽  
...  
Keyword(s):  
Early Embryogenesis ◽  
Alternative Promoter ◽  
Germ Layers ◽  
Promoter Usage ◽  
Whole Transcriptome

Alternative promoter usage and alternative splicing contribute to mRNA heterogeneity of mouse monocarboxylate transporter 2

2007 ◽  
Vol 32 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Shelley X. L. Zhang ◽  
Tina R. Searcy ◽  
Yiman Wu ◽  
David Gozal ◽  
Yang Wang
Keyword(s):  
Transcription Factors ◽  
Alternative Splicing ◽  
Alternative Promoter ◽  
Monocarboxylate Transporter ◽  
Specific Expression ◽  
Exon 2 ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Exon 1 ◽  
Promoter Usage

Expression patterns of monocarboxylate transporter 2 (MCT2) display mRNA diversity in a tissue-specific fashion. We cloned and characterized multiple mct2 5′-cDNA ends from the mouse and determined the structural organization of the mct2 gene. We found that transcription of this gene was initiated from five independent genomic regions that spanned >80 kb on chromosome 10, resulting in five unique exon 1 variants (exons 1a, 1b, 1c, 1d, and 1e) that were then spliced to the common exon 2. Alternative splicing of four internal exons (exons AS1, AS2, AS3, and exon 3) greatly increased the complexity of mRNA diversity. While exon 1c was relatively commonly used for transcription initiation in various tissues, other exon 1 variants were used in a tissue-specific fashion, especially exons 1b and 1d that were used exclusively for testis-specific expression. Sequence analysis of 5′-flanking regions upstream of exons 1a, 1b, and 1c revealed the presence of numerous potential binding sites for ubiquitous transcription factors in all three regions and for transcription factors implicated in testis-specific or hypoxia-induced gene expression in the 1b region. Transient transfection assays demonstrated that each of the three regions contained a functional promoter and that the in vitro, cell type-specific activities of these promoters were consistent with the tissue-specific expression pattern of the mct2 gene in vivo. These results indicate that tissue-specific expression of the mct2 gene is controlled by multiple alternative promoters and that both alternative promoter usage and alternative splicing contribute to the remarkable mRNA diversity of the gene.

scholarly journals Heritable, Allele-Specific Chromosomal Looping between Tandem Promoters Specifies Promoter Usage of SHC1

2018 ◽  
Vol 38 (9) ◽  
Author(s):  
Xichuan Li ◽  
Zhenzhen Lin ◽  
Hao Wang ◽  
Dan Zhao ◽  
Xing Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Chromatin Structure ◽  
Molecular Mechanisms ◽  
Peripheral Blood Lymphocytes ◽  
Alternative Promoter ◽  
Alternative Promoters ◽  
Transcription Pattern ◽  
Upstream Promoter ◽  
Allele Specific ◽  
Promoter Usage

ABSTRACT One-half of the genes in the human genome contain alternative promoters, some of which generate products with opposing functions. Aberrant silencing or activation of such alternative promoters is associated with multiple diseases, including cancer, but little is known regarding the molecular mechanisms that control alternative promoter choice. The SHC1 gene encodes p46 Shc /p52 Shc and p66 Shc , proteins oppositely regulating anchorage-independent growth that are produced by transcription initiated from the upstream and downstream tandem promoters of SHC1 , respectively. Here we demonstrate that activation of these promoters is mutually exclusive on separate alleles in single primary endothelial cells in a heritable fashion, ensuring expression of both transcripts by the cell. Peripheral blood lymphocytes that do not transcribe p66 Shc transcribed p52 Shc biallelically. This distinct monoallelic transcription pattern is established by allele-specific chromosomal looping between tandem promoters, which silences the upstream promoter. Our results reveal a new mechanism to control alternative promoter usage through higher-order chromatin structure.

scholarly journals Alternative Promoter Usage at the Notch1 Locus Supports Ligand-Independent Signaling in T Cell Development and Leukemogenesis

Immunity ◽  
2010 ◽  
Vol 33 (5) ◽  
pp. 685-698 ◽  
Author(s):  
Pablo Gómez-del Arco ◽  
Mariko Kashiwagi ◽  
Audrey F. Jackson ◽  
Taku Naito ◽  
Jiangwen Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Alternative Promoter ◽  
Promoter Usage

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.

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