scholarly journals Genetic structure of the abd-A gene of Drosophila

Development ◽  
1989 ◽  
Vol 107 (3) ◽  
pp. 575-583 ◽  
Author(s):  
A. Busturia ◽  
J. Casanova ◽  
E. Sanchez-Herrero ◽  
R. Gonzalez ◽  
G. Morata
Keyword(s):  
Genetic Structure ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Transcription Unit ◽  
Bithorax Complex ◽  
Coding Region ◽  
Regulatory Regions ◽  
Protein Coding ◽  
Spatial Regulation ◽  
Correct Level

We report the embryonic and adult phenotypes of a number of mutations of the abd-A gene of the bithorax complex. Some of them result in loss of abd-A function in the whole abd-A domain and are usually lethal. These probably eliminate or inactivate abd-A protein products. Other mutations affect only part of the abd-A domain. These are viable, appear to map outside the abd-A transcription unit, and presumably alter the normal spatial regulation of abd-A products. We propose a model of abd-A structure based on a protein-coding region and two cis-regulatory regions. Regulatory region 1, 3′ to the transcription unit, contains positive and negative regulatory elements. Regulatory region 2, 5′ to the transcription unit, establishes the correct level of abd-A activity in the abdominal metameres.

The gene for the heat-shock protein 70 of Euplotes focardii, an Antarctic psychrophilic ciliate

2004 ◽  
Vol 16 (1) ◽  
pp. 23-28 ◽  
Author(s):  
ANTONIETTA LA TERZA ◽  
CRISTINA MICELI ◽  
PIERANGELO LUPORINI
Keyword(s):  
Thermal Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Specific Response ◽  
Hsp70 Gene ◽  
Sequence Motifs ◽  
Coding Region

In the Antarctic ciliate, Euplotes focardii, the heat-shock protein 70 (Hsp70) gene does not show any appreciable activation by a thermal stress. Yet, it is activated to appreciable transcriptional levels by oxidative and chemical stresses, thus implying that it evolved a mechanism of selective, stress-specific response. A basic step in investigating this mechanism is the determination of the complete nucleotide sequence of the E. focardii Hsp70 gene. This gene contains a coding region specific for an Hsp70 protein that carries unique amino acid substitutions of potential significance for cold adaptation, and a 5' regulatory region that includes sequence motifs denoting two distinct types of stress-inducible promoters, known as “Heat Shock Elements” (HSE) and “Stress Response Elements” (StRE). From the study of the interactions of these regulatory elements with their specific transactivator factors we expect to shed light on the adaptive modifications that prevent the Hsp70 gene of E. focardii from responding to thermal stress while being responsive to other stresses.

Analysis of the human CD10/neutral endopeptidase 24.11 promoter region: two separate regulatory elements

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3199-3207 ◽  
Author(s):  
F Ishimaru ◽  
MA Shipp
Keyword(s):  
Binding Sites ◽  
Lymphoblastic Leukemia ◽  
Regulatory Region ◽  
Neutral Endopeptidase ◽  
Regulatory Elements ◽  
Control Element ◽  
Regulatory Regions ◽  
Endopeptidase 24.11

The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) is expressed on normal and malignant lymphoid progenitors, granulocytes, and a variety of epithelial cells. To further define the tissue-specific and developmentally related expression of CD10/NEP, we have characterized two separate regulatory regions that control the transcription of 5′ alternatively spliced CD10/NEP transcripts. These type 1 and 2 CD10/NEP regulatory regions are both characterized by the presence of multiple transcription initiation sites and the absence of classic TATA boxes and consensus initiator elements. The purine-rich type 1 regulatory region, which includes 5′ UTR exon 1 sequence, is characterized by multiple putative PU.1 binding sites and consensus ets-binding motifs. In marked contrast, the GC-rich type 2 regulatory region contains multiple putative Sp1 binding sites, a potential consensus retinoblastoma control element (RCE), and an inverted CCAAT box. In the majority of tissues examined to date, type 2 CD10/NEP transcripts were more abundant; the abundance of type 1 transcripts was more variable, with the highest type 1 levels in fetal thymus and certain lymphoblastic leukemia cell lines.

scholarly journals Structure of transcripts from the homeotic Antennapedia gene of Drosophila melanogaster: two promoters control the major protein-coding region.

1986 ◽  
Vol 6 (12) ◽  
pp. 4676-4689 ◽  
Author(s):  
A Laughon ◽  
A M Boulet ◽  
J R Bermingham ◽  
R A Laymon ◽  
M P Scott
Keyword(s):  
Drosophila Melanogaster ◽  
Alternative Polyadenylation ◽  
Transcription Unit ◽  
Cdna Clones ◽  
Major Protein ◽  
Coding Region ◽  
Developmentally Regulated ◽  
Protein Coding ◽  
Reading Frame ◽  
C Terminus

The Antennapedia (Antp) homeotic gene of Drosophila melanogaster regulates segmental identity in the thorax. Loss of Antp function results in altered development of the embryonic thoracic segments or can cause legs to be transformed into antennae. Certain combinations of Antp recessive lethal alleles complement to permit normal development. The structure of the Antp gene, analyzed by sequencing cDNA clones and exons and by transcript mapping, revealed some of the basis for its genetic complexity. It has two promoters governing two nested transcription units, one unit 36 and one 103 kilobase pairs (kb) long. Both units incorporated the same protein-coding exons, all of which are located in the 3'-most 13 kb of the gene. The two promoters resulted in the attachment of either of two long noncoding leader sequences (1.5 and 1.7 kb) to a 1.1-kb open reading frame. Both transcription units used the same pair of alternative polyadenylation sites 1.4 kb apart; the choice of sites was developmentally regulated. Some of the mutations that disrupt the larger transcription unit complemented a mutation affecting the smaller one. Dominant mutations that transform antennae into legs split the gene but left the coding exons intact. The encoded protein has unusually long runs of glutamine and a homeodomain near the C terminus.

scholarly journals Candidate cancer driver mutations in superenhancers and long-range chromatin interaction networks

2017 ◽  
Author(s):  
Lina Wadi ◽  
Liis Uusküla-Reimand ◽  
Keren Isaev ◽  
Shimin Shuai ◽  
Vincent Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Target Genes ◽  
Tumor Biology ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Driver Mutations ◽  
Regulatory Regions ◽  
Protein Coding ◽  
Primary Tumors

AbstractA comprehensive catalogue of the mutations that drive tumorigenesis and progression is essential to understanding tumor biology and developing therapies. Protein-coding driver mutations have been well-characterized by large exome-sequencing studies, however many tumors have no mutations in protein-coding driver genes. Non-coding mutations are thought to explain many of these cases, however few non-coding drivers besides TERT promoter are known. To fill this gap, we analyzed 150,000 cis-regulatory regions in 1,844 whole cancer genomes from the ICGC-TCGA PCAWG project. Using our new method, ActiveDriverWGS, we found 41 frequently mutated regulatory elements (FMREs) enriched in non-coding SNVs and indels (FDR<0.05) characterized by aging-associated mutation signatures and frequent structural variants. Most FMREs are distal from genes, reported here for the first time and also recovered by additional driver discovery methods. FMREs were enriched in super-enhancers, H3K27ac enhancer marks of primary tumors and long-range chromatin interactions, suggesting that the mutations drive cancer by distally controlling gene expression through threedimensional genome organization. In support of this hypothesis, the chromatin interaction network of FMREs and target genes revealed associations of mutations and differential gene expression of known and novel cancer genes (e.g., CNNB1IP1, RCC1), activation of immune response pathways and altered enhancer marks. Thus distal genomic regions may include additional, infrequently mutated drivers that act on target genes via chromatin loops. Our study is an important step towards finding such regulatory regions and deciphering the somatic mutation landscape of the non-coding genome.

scholarly journals ChIP-GSM: Inferring active transcription factor modules to predict functional regulatory elements

2021 ◽  
Vol 17 (7) ◽  
pp. e1009203
Author(s):  
Xi Chen ◽  
Andrew F. Neuwald ◽  
Leena Hilakivi-Clarke ◽  
Robert Clarke ◽  
Jianhua Xuan
Keyword(s):  
Regulatory Region ◽  
K562 Cells ◽  
Regulatory Elements ◽  
Binding Potential ◽  
Regulatory Regions ◽  
Cellular Processes ◽  
Weak Binding ◽  
Active Transcription ◽  
Activate Gene

Transcription factors (TFs) often function as a module including both master factors and mediators binding at cis-regulatory regions to modulate nearby gene transcription. ChIP-seq profiling of multiple TFs makes it feasible to infer functional TF modules. However, when inferring TF modules based on co-localization of ChIP-seq peaks, often many weak binding events are missed, especially for mediators, resulting in incomplete identification of modules. To address this problem, we develop a ChIP-seq data-driven Gibbs Sampler to infer Modules (ChIP-GSM) using a Bayesian framework that integrates ChIP-seq profiles of multiple TFs. ChIP-GSM samples read counts of module TFs iteratively to estimate the binding potential of a module to each region and, across all regions, estimates the module abundance. Using inferred module-region probabilistic bindings as feature units, ChIP-GSM then employs logistic regression to predict active regulatory elements. Validation of ChIP-GSM predicted regulatory regions on multiple independent datasets sharing the same context confirms the advantage of using TF modules for predicting regulatory activity. In a case study of K562 cells, we demonstrate that the ChIP-GSM inferred modules form as groups, activate gene expression at different time points, and mediate diverse functional cellular processes. Hence, ChIP-GSM infers biologically meaningful TF modules and improves the prediction accuracy of regulatory region activities.

Evolutionary conservation of homeodomain-binding sites and other sequences upstream and within the major transcription unit of the Drosophila segmentation gene engrailed

1989 ◽  
Vol 9 (10) ◽  
pp. 4304-4311
Author(s):  
J A Kassis ◽  
C Desplan ◽  
D K Wright ◽  
P H O'Farrell
Keyword(s):  
Binding Sites ◽  
Regulatory Region ◽  
Divergence Time ◽  
Evolutionary Conservation ◽  
Transcription Unit ◽  
Regulatory Proteins ◽  
Coding Region ◽  
Cis Acting ◽  
Perfect Sequence ◽  
Development Proceeds

The engrailed (en) gene functions throughout Drosophila development and is expressed in a succession of intricate spatial patterns as development proceeds. Normal en function relies on an extremely large cis-acting regulatory region (70 kilobases). We are using evolutionary conservation to help identify en sequences important in regulating patterned expression. Sequence comparison of 2.6 kilobases upstream of the en coding region of D. melanogaster and D. virilis (estimated divergence time, 60 million years) showed that 30% of this DNA occurs in islands of near perfect sequence conservation. One of these conserved islands contains binding sites for homeodomain-containing proteins. It has been shown genetically that homeodomain-containing proteins regulate en expression. Our data suggested that this regulation may be direct. The remaining conserved islands may contain binding sites for other regulatory proteins.

Structure of transcripts from the homeotic Antennapedia gene of Drosophila melanogaster: two promoters control the major protein-coding region

1986 ◽  
Vol 6 (12) ◽  
pp. 4676-4689
Author(s):  
A Laughon ◽  
A M Boulet ◽  
J R Bermingham ◽  
R A Laymon ◽  
M P Scott
Keyword(s):  
Drosophila Melanogaster ◽  
Alternative Polyadenylation ◽  
Transcription Unit ◽  
Cdna Clones ◽  
Major Protein ◽  
Coding Region ◽  
Developmentally Regulated ◽  
Protein Coding ◽  
Reading Frame ◽  
C Terminus

The Antennapedia (Antp) homeotic gene of Drosophila melanogaster regulates segmental identity in the thorax. Loss of Antp function results in altered development of the embryonic thoracic segments or can cause legs to be transformed into antennae. Certain combinations of Antp recessive lethal alleles complement to permit normal development. The structure of the Antp gene, analyzed by sequencing cDNA clones and exons and by transcript mapping, revealed some of the basis for its genetic complexity. It has two promoters governing two nested transcription units, one unit 36 and one 103 kilobase pairs (kb) long. Both units incorporated the same protein-coding exons, all of which are located in the 3'-most 13 kb of the gene. The two promoters resulted in the attachment of either of two long noncoding leader sequences (1.5 and 1.7 kb) to a 1.1-kb open reading frame. Both transcription units used the same pair of alternative polyadenylation sites 1.4 kb apart; the choice of sites was developmentally regulated. Some of the mutations that disrupt the larger transcription unit complemented a mutation affecting the smaller one. Dominant mutations that transform antennae into legs split the gene but left the coding exons intact. The encoded protein has unusually long runs of glutamine and a homeodomain near the C terminus.

scholarly journals Structure and function of RNA elements present in enteroviral genomes

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Mariola Dutkiewicz ◽  
Aleksandra Stachowiak ◽  
Agata Swiatkowska ◽  
Jerzy Ciesiołka
Keyword(s):  
Regulatory Elements ◽  
Structure And Function ◽  
Host Cells ◽  
Rna Structures ◽  
Coding Region ◽  
Protein Coding ◽  
Reading Frame ◽  
Noncoding Regions ◽  
Long Time ◽  
And Function

Enteroviruses are small RNA(+) viruses that encode one open reading frame flanked by two extensive noncoding regions carrying structural RNA regulatory elements that control replication and translation processes. For a long time the central, coding region was thought to remain single-stranded and its only function was supposed to be as the template for polyprotein synthesis. It turned out, however, that the protein coding region also encodes important RNA structures crucial for the viral life cycle and virus persistence in host cells. This review considers the RNA structures in enteroviral genomes identified and characterized to date.

Regulatory regions of SERPINC1 gene: Identification of the first mutation associated with antithrombin deficiency

2012 ◽  
Vol 107 (03) ◽  
pp. 430-437 ◽  
Author(s):  
María de la Morena-Barrio ◽  
Ana Antón ◽  
Irene Martínez-Martínez ◽  
José Padilla ◽  
Antonia Miñano ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Promoter Region ◽  
Regulatory Region ◽  
Type I ◽  
Coding Region ◽  
Gene Encoding ◽  
Antithrombin Deficiency ◽  
Regulatory Regions ◽  
Phenotype Analysis ◽  
Potential Promoter

SummaryAntithrombin is the main endogenous anticoagulant. Impaired function or deficiency of this molecule significantly increases the risk of thrombosis. We studied the genetic variability of SERPINC1, the gene encoding antithrombin, to identify mutations affecting regulatory regions with functional effect on its levels. We sequenced 15,375 bp of this gene, including the potential promoter region, in three groups of subjects: five healthy subjects with antithrombin levels in the lowest (75%) and highest (115%) ranges of our population, 14 patients with venous thrombosis and a moderate antithrombin deficiency as the single thrombophilic defect, and two families with type I antithrombin deficiency who had neither mutations affecting exons or flanking regions, nor gross gene deletions. Our study confirmed the low genetic variability of SERPINC1, particularly in the coding region, and its minor influence in the heterogeneity of antithrombin levels. Interestingly, in one family, we identified a g.2143 C>G transversion, located 170 bp upstream from the translation initiation codon. This mutation affected one of the four regions located in the minimal promoter that have potential regulatory activity according to previous DNase footprinting protection assays. Genotype-phenotype analysis in the affected family and reporter analysis in different hepatic cell lines demonstrated that this mutation significantly impaired, although it did not abolish, the downstream transcription. Therefore, this is the first mutation affecting a regulatory region of the SERPINC1 gene associated with antithrombin deficiency. Our results strongly sustain the inclusion of the promoter region of SERPINC1 in the molecular analysis of patients with antithrombin deficiency.

scholarly journals Evolutionary conservation of homeodomain-binding sites and other sequences upstream and within the major transcription unit of the Drosophila segmentation gene engrailed.

1989 ◽  
Vol 9 (10) ◽  
pp. 4304-4311 ◽  
Author(s):  
J A Kassis ◽  
C Desplan ◽  
D K Wright ◽  
P H O'Farrell
Keyword(s):  
Binding Sites ◽  
Regulatory Region ◽  
Divergence Time ◽  
Evolutionary Conservation ◽  
Transcription Unit ◽  
Regulatory Proteins ◽  
Coding Region ◽  
Cis Acting ◽  
Perfect Sequence ◽  
Development Proceeds

The engrailed (en) gene functions throughout Drosophila development and is expressed in a succession of intricate spatial patterns as development proceeds. Normal en function relies on an extremely large cis-acting regulatory region (70 kilobases). We are using evolutionary conservation to help identify en sequences important in regulating patterned expression. Sequence comparison of 2.6 kilobases upstream of the en coding region of D. melanogaster and D. virilis (estimated divergence time, 60 million years) showed that 30% of this DNA occurs in islands of near perfect sequence conservation. One of these conserved islands contains binding sites for homeodomain-containing proteins. It has been shown genetically that homeodomain-containing proteins regulate en expression. Our data suggested that this regulation may be direct. The remaining conserved islands may contain binding sites for other regulatory proteins.

Sign in / Sign up

Export Citation Format

Share Document