scholarly journals VDAC Genes Expression and Regulation in Mammals

2021 ◽  
Vol 12 ◽  
Author(s):  
Federica Zinghirino ◽  
Xena Giada Pappalardo ◽  
Angela Messina ◽  
Giuseppe Nicosia ◽  
Vito De Pinto ◽  
...  
Keyword(s):  
Homo Sapiens ◽  
Functional Divergence ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Translation Regulation ◽  
Mitochondrial Outer Membrane ◽  
Core Promoters ◽  
Mouse Tissues ◽  
Proliferation And Differentiation ◽  
Pore Forming Proteins

VDACs are pore-forming proteins, coating the mitochondrial outer membrane, and playing the role of main regulators for metabolites exchange between cytosol and mitochondria. In mammals, three isoforms have evolutionary originated, VDAC1, VDAC2, and VDAC3. Despite similarity in sequence and structure, evidence suggests different biological roles in normal and pathological conditions for each isoform. We compared Homo sapiens and Mus musculus VDAC genes and their regulatory elements. RNA-seq transcriptome analysis shows that VDAC isoforms are expressed in human and mouse tissues at different levels with a predominance of VDAC1 and VDAC2 over VDAC3, with the exception of reproductive system. Numerous transcript variants for each isoform suggest specific context-dependent regulatory mechanisms. Analysis of VDAC core promoters has highlighted that, both in a human and a mouse, VDAC genes show features of TATA-less ones. The level of CG methylation of the human VDAC genes revealed that VDAC1 promoter is less methylated than other two isoforms. We found that expression of VDAC genes is mainly regulated by transcription factors involved in controlling cell growth, proliferation and differentiation, apoptosis, and bioenergetic metabolism. A non-canonical initiation site termed “the TCT/TOP motif,” the target for translation regulation by the mTOR pathway, was identified in human VDAC2 and VDAC3 and in every murine VDACs promoter. In addition, specific TFBSs have been identified in each VDAC promoter, supporting the hypothesis that there is a partial functional divergence. These data corroborate our experimental results and reinforce the idea that gene regulation could be the key to understanding the evolutionary specialization of VDAC isoforms.

scholarly journals Genomic organization and chromosomal localization of the mouse synexin gene

1994 ◽  
Vol 301 (3) ◽  
pp. 835-845 ◽  
Author(s):  
Z Y Zhang-Keck ◽  
M Srivastava ◽  
C A Kozak ◽  
H Caohuy ◽  
A Shirvan ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Gene Encoding ◽  
S1 Nuclease ◽  
Mapping Sequence ◽  
Mouse Tissues ◽  
Potential Promoter ◽  
Flanking Region ◽  
Nuclease Mapping

We have isolated and characterized the gene encoding mouse synexin, which consists of 14 exons and spans approximately 30 kbp of genomic DNA. The protein's unique N-terminal domain is encoded by six exons, and the C-terminal tetrad repeat, the site of the membrane-fusion and ion-channel domain, is encoded by seven exons. The first exon encodes the 5′-untranslated region. Analysis of synexin-gene expression in different mouse tissues shows that mRNA with exon 6 is only present in brain, heart and skeletal muscle. mRNA lacking exon 6 is expressed in all tissues we have examined. The initiation site for transcription was determined by primer-extension analysis and S1 nuclease mapping. Sequence analysis of the 1.3 kb 5′-flanking region revealed that the promoter has a TATA box located at position -25 and a number of potential promoter and regulatory elements. A CCAAT motif was not observed but CCATT is located in an appropriate position for the CCAAT motif upstream from the transcription-initiation start site. In addition, the 5′-flanking region contains two sets of palindromic sequences. Finally, we have determined that the functional synexin gene (Anx7) is located on mouse chromosome 14 and that a pseudogene (Anx7-ps1) is located on chromosome 10.

scholarly journals Genome-wide characterization of MATE gene family and expression profiles in response to abiotic stresses in rice (Oryza sativa)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhixuan Du ◽  
Qitao Su ◽  
Zheng Wu ◽  
Zhou Huang ◽  
Jianzhong Bao ◽  
...  
Keyword(s):  
Oryza Sativa ◽  
Gene Family ◽  
Tandem Repeats ◽  
Expression Profiles ◽  
Functional Divergence ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Genome Wide ◽  
Comprehensive Information ◽  
Family Gene

AbstractMultidrug and toxic compound extrusion (MATE) proteins are involved in many physiological functions of plant growth and development. Although an increasing number of MATE proteins have been identified, the understanding of MATE proteins is still very limited in rice. In this study, 46 MATE proteins were identified from the rice (Oryza sativa) genome by homology searches and domain prediction. The rice MATE family was divided into four subfamilies based on the phylogenetic tree. Tandem repeats and fragment replication contribute to the expansion of the rice MATE gene family. Gene structure and cis-regulatory elements reveal the potential functions of MATE genes. Analysis of gene expression showed that most of MATE genes were constitutively expressed and the expression patterns of genes in different tissues were analyzed using RNA-seq. Furthermore, qRT-PCR-based analysis showed differential expression patterns in response to salt and drought stress. The analysis results of this study provide comprehensive information on the MATE gene family in rice and will aid in understanding the functional divergence of MATE genes.

scholarly journals Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms

2006 ◽  
Vol 128 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Rocio K. Finol-Urdaneta ◽  
Nina Strüver ◽  
Heinrich Terlau
Keyword(s):  
Translation Initiation ◽  
Cell Function ◽  
Functional Divergence ◽  
Initiation Site ◽  
Translation Initiation Site ◽  
Inactivation Kinetics ◽  
Mouse Heart ◽  
Redox Stress ◽  
Redox Modulation ◽  
Stress States

Ion channels are membrane-spanning proteins that allow ions to permeate at high rates. The kinetic characteristics of the channels present in a cell determine the cell signaling profile and therefore cell function in many different physiological processes. We found that Kv1.7 channels from mouse heart muscle have two putative translation initiation start sites that generate two channel isoforms with different functional characteristics, mKv1.7L (489 aa) and a shorter mKv1.7S (457 aa). The electrophysiological analysis of mKv1.7L and mKv1.7S channels revealed that the two channel isoforms have different inactivation kinetics. The channel resulting from the longer protein (L) inactivates faster than the shorter channels (S). Our data supports the hypothesis that mKv1.7L channels inactivate predominantly due to an N-type related mechanism, which is impaired in the mKv1.7S form. Furthermore, only the longer version mKv1.7L is regulated by the cell redox state, whereas the shorter form mKv1.7S is not. Thus, expression starting at each translation initiation site results in significant functional divergence. Our data suggest that the redox modulation of mKv1.7L may occur through a site in the cytoplasmic N-terminal domain that seems to encompass a metal coordination motif resembling those found in many redox-sensitive proteins. The mRNA expression profile and redox modulation of mKv1.7 kinetics identify these channels as molecular entities of potential importance in cellular redox-stress states such as hypoxia.

Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene

1988 ◽  
Vol 8 (7) ◽  
pp. 2896-2909 ◽  
Author(s):  
E A Sternberg ◽  
G Spizz ◽  
W M Perry ◽  
D Vizard ◽  
T Weil ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Regulatory Element ◽  
Simian Virus 40 ◽  
Muscle Cells ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Simian Virus ◽  
Cell Type ◽  
Specific Expression ◽  
Developing Muscle

Terminal differentiation of skeletal myoblasts is accompanied by induction of a series of tissue-specific gene products, which includes the muscle isoenzyme of creatine kinase (MCK). To begin to define the sequences and signals involved in MCK regulation in developing muscle cells, the mouse MCK gene has been isolated. Sequence analysis of 4,147 bases of DNA surrounding the transcription initiation site revealed several interesting structural features, some of which are common to other muscle-specific genes and to cellular and viral enhancers. To test for sequences required for regulated expression, a region upstream of the MCK gene from -4800 to +1 base pairs, relative to the transcription initiation site, was linked to the coding sequences of the bacterial chloramphenicol acetyltransferase (CAT) gene. Introduction of this MCK-CAT fusion gene into C2 muscle cells resulted in high-level expression of CAT activity in differentiated myotubes and no detectable expression in proliferating undifferentiated myoblasts or in nonmyogenic cell lines. Deletion mutagenesis of sequences between -4800 and the transcription start site showed that the region between -1351 and -1050 was sufficient to confer cell type-specific and developmentally regulated expression on the MCK promoter. This upstream regulatory element functioned independently of position, orientation, or distance from the promoter and therefore exhibited the properties of a classical enhancer. This upstream enhancer also was able to confer muscle-specific regulation on the simian virus 40 promoter, although it exhibited a 3- to 5-fold preference for its own promoter. In contrast to the cell type- and differentiation-specific expression of the upstream enhancer, the MCK promoter was able to function in myoblasts and myotubes and in nonmyogenic cell lines when combined with the simian virus 40 enhancer. An additional positive regulatory element was identified within the first intron of the MCK gene. Like the upstream enhancer, this intragenic element functioned independently of position, orientation, and distance with respect to the MCK promoter and was active in differentiated myotubes but not in myoblasts. These results demonstrate that expression of the MCK gene in developing muscle cells is controlled by complex interactions among multiple upstream and intragenic regulatory elements that are functional only in the appropriate cellular context.

The Long Road to Understanding RNAPII Transcription Initiation and Related Syndromes

2021 ◽  
Vol 90 (1) ◽  
pp. 193-219
Author(s):  
Emmanuel Compe ◽  
Jean-Marc Egly
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Transcription Initiation ◽  
Rna Synthesis ◽  
Regulatory Elements ◽  
Initiation Mechanism ◽  
Protein Coding ◽  
Core Promoters ◽  
General Transcription Factors

In eukaryotes, transcription of protein-coding genes requires the assembly at core promoters of a large preinitiation machinery containing RNA polymerase II (RNAPII) and general transcription factors (GTFs). Transcription is potentiated by regulatory elements called enhancers, which are recognized by specific DNA-binding transcription factors that recruit cofactors and convey, following chromatin remodeling, the activating cues to the preinitiation complex. This review summarizes nearly five decades of work on transcription initiation by describing the sequential recruitment of diverse molecular players including the GTFs, the Mediator complex, and DNA repair factors that support RNAPII to enable RNA synthesis. The elucidation of the transcription initiation mechanism has greatly benefited from the study of altered transcription components associated with human diseases that could be considered transcription syndromes.

scholarly journals Identification and characterization of cis-regulatory elements for photoreceptor type-specific transcription in zebrafish

2019 ◽  
Author(s):  
Wei Fang ◽  
Yi Wen ◽  
Xiangyun Wei
Keyword(s):  
Core Promoter ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Protein Coding ◽  
Core Promoters ◽  
Protein Coding Genes ◽  
The Core ◽  
Cell Type Specific ◽  
Identification And Characterization

AbstractTissue-specific or cell type-specific transcription of protein-coding genes is controlled by both trans-regulatory elements (TREs) and cis-regulatory elements (CREs). However, it is challenging to identify TREs and CREs, which are unknown for most genes. Here, we describe a protocol for identifying two types of transcription-activating CREs—core promoters and enhancers—of zebrafish photoreceptor type-specific genes. This protocol is composed of three phases: bioinformatic prediction, experimental validation, and characterization of the CREs. To better illustrate the principles and logic of this protocol, we exemplify it with the discovery of the core promoter and enhancer of the mpp5b apical polarity gene (also known as ponli), whose red, green, and blue (RGB) cone-specific transcription requires its enhancer, a member of the rainbow enhancer family. While exemplified with an RGB cone-specific gene, this protocol is general and can be used to identify the core promoters and enhancers of other protein-coding genes.

scholarly journals Transcription start site analysis reveals widespread divergent transcription in D. melanogaster and core promoter-encoded enhancer activities

2017 ◽  
Author(s):  
Sarah Rennie ◽  
Maria Dalby ◽  
Marta Lloret-Llinares ◽  
Stylianos Bakoulis ◽  
Christian Dalager Vaagensø ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Core Promoter ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Promoter Strength ◽  
Gene Promoters ◽  
Core Promoters ◽  
Promoter Architecture ◽  
Regulatory Functions

ABSTRACTMammalian gene promoters and enhancers share many properties. They are composed of a unified promoter architecture of divergent transcripton initiation and gene promoters may exhibit enhancer function. However, it is currently unclear how expression strength of a regulatory element relates to its enhancer strength and if the unifying architecture is conserved across Metazoa. Here we investigate the transcription initiation landscape and its associated RNA decay in D. melanogaster. Surprisingly, we find that the majority of active gene-distal enhancers and a considerable fraction of gene promoters are divergently transcribed. We observe quantitative relationships between enhancer potential, expression level and core promoter strength, providing an explanation for indirectly related histone modifications that are reflecting expression levels. Lowly abundant unstable RNAs initiated from weak core promoters are key characteristics of gene-distal developmental enhancers, while the housekeeping enhancer strengths of gene promoters reflect their expression strengths. The different layers of regulation mediated by gene-distal enhancers and gene promoters are also reflected in chromatin interaction data. Our results suggest a unified promoter architecture of many D. melanogaster regulatory elements, that is universal across Metazoa, whose regulatory functions seem to be related to their core promoter elements.

scholarly journals Characterization of two atypical promoters and alternate mRNA processing in the mouse Thy-1.2 glycoprotein gene.

1986 ◽  
Vol 6 (8) ◽  
pp. 2923-2931 ◽  
Author(s):  
H A Ingraham ◽  
G A Evans
Keyword(s):  
Genomic Sequence ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Lymphoid Cells ◽  
Gene Encoding ◽  
Specific Expression ◽  
Transcriptional Initiation ◽  
Glycoprotein Gene ◽  
Cell Type Specific Expression ◽  
Flanking Region

The promoter and 5' flanking region of the mouse Thy-1.2 glycoprotein gene were characterized by DNA sequencing, primer extension analysis, and deletion analysis. Transcriptional initiation sites were identified which corresponded to two separate exons upstream of the portion of the gene encoding the Thy-1.2 glycoprotein. We demonstrated that the mouse Thy-1.2 gene was transcribed from two atypical promoters separated by 260 base pairs in the genomic sequence. These promoters contained neither TATAAG nor GGPyCCAATCT homologous sequences but defined a conserved nonamer CTCCCTGCT at -48 from each initiation site. Two Thy-1.2 mRNA species of 1,835 and 1,939 nucleotides, differing in the 5' untranslated region of the mRNA, were thus transcribed from the single Thy-1.2 gene by mRNA splicing to the same downstream exon. Recombinant genomes in which the bacterial chloramphenicol acetyltransferase gene was expressed from either of the two Thy-1.2 promoters demonstrated that each promoter functioned independently and did not direct cell-specific expression in lymphoid cells. The 5' flanking region of the Thy-1.2 gene upstream of -68 could be eliminated without altering cell-type-specific expression. This suggests that regulatory elements responsible for tissue and developmental stage-specific expression of the Thy-1.2 gene are not present in the 5' flanking DNA but may reside downstream of the promoters.

scholarly journals Interactions of the Antizyme AtoC with Regulatory Elements of the Escherichia coli atoDAEB Operon

2007 ◽  
Vol 189 (17) ◽  
pp. 6324-6332 ◽  
Author(s):  
Meropi K. Matta ◽  
Efthimia E. Lioliou ◽  
Cynthia H. Panagiotidis ◽  
Dimitrios A. Kyriakidis ◽  
Christos A. Panagiotidis
Keyword(s):  
Escherichia Coli ◽  
Transcription Initiation ◽  
Response Regulator ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Integration Host Factor ◽  
Chemical Mutagenesis ◽  
Dual Function

ABSTRACT AtoC has a dual function as both an antizyme, the posttranslational inhibitor of polyamine biosynthetic enzymes, and the transcriptional regulator of genes involved in short-chain fatty acid catabolism (the atoDAEB operon). We have previously shown that AtoC is the response regulator of the AtoS-AtoC two-component signal transduction system that activates atoDAEB when Escherichia coli is exposed to acetoacetate. Here, we show that the same cis elements control both promoter inducibility and AtoC binding. Chromatin immunoprecipitation experiments confirmed the acetoacetate-inducible binding of AtoC to the predicted DNA region in vivo. DNase I protection footprinting analysis revealed that AtoC binds two 20-bp stretches, constituting an inverted palindrome, that are located at −146 to −107 relative to the transcription initiation site. Analyses of promoter mutants obtained by in vitro chemical mutagenesis of the atoDAEB promoter verified both the importance of AtoC binding for the inducibility of the promoter by acetoacetate and the σ54 dependence of atoDAEB expression. The integration host factor was also identified as a critical component of the AtoC-mediated induction of atoDAEB.

scholarly journals Genomic organization and transcriptional analysis of the human l-glutaminase gene

2003 ◽  
Vol 370 (3) ◽  
pp. 771-784 ◽  
Author(s):  
Cristina PÉREZ-GÓMEZ ◽  
José M. MATÉS ◽  
Pedro M. GÓMEZ-FABRE ◽  
Antonio del CASTILLO-OLIVARES ◽  
Francisco J. ALONSO ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Genomic Organization ◽  
Core Promoter ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Genome Project ◽  
Transcriptional Analysis ◽  
Cdna Clones ◽  
Mobility Shift ◽  
Specific Expression

In mammals, glutaminase (GA) is expressed in most tissues, but the regulation of organ-specific expression is largely unknown. Therefore, as an essential step towards studying the regulation of GA expression, the human liver-type GA (hLGA) gene has been characterized. LGA genomic sequences were isolated using the genome walking technique. Analysis and comparison of these sequences with two LGA cDNA clones and the Human Genome Project database, allowed the determination of the genomic organization of the LGA gene. The gene has 18 exons and is approx. 18kb long. All exon/intron junction sequences conform to the GT/AG rule. Progressive deletion analysis of LGA promoter—luciferase constructs indicated that the core promoter is located between nt −141 and +410, with several potential regulatory elements: CAAT, GC, TATA-like, Ras-responsive element binding protein and specificity protein 1 (Sp1) sites. The minimal promoter was mapped within +107 and +410, where only an Sp1 binding site is present. Mutation experiments suggested that two CAAT recognition elements near the transcription-initiation site (-138 and −87), play a crucial role for optimal promoter activity. Electrophoretic mobility-shift assays confirmed the importance of CAAT- and TATA-like boxes to enhance basal transcription, and demonstrated that HNF-1 motif is a significant distal element for transcriptional regulation of the hLGA gene.

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