scholarly journals Transcriptional and Posttranscriptional Regulations of theHLA-GGene

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Erick C. Castelli ◽  
Luciana C. Veiga-Castelli ◽  
Layale Yaghi ◽  
Philippe Moreau ◽  
Eduardo A. Donadi
Keyword(s):  
Promoter Region ◽  
Hla Class I ◽  
Regulatory Elements ◽  
Class I ◽  
Proximal Promoter ◽  
Null Alleles ◽  
Gene Control ◽  
Coding Region ◽  
Synonymous Mutations ◽  
Classical Class

HLA-Ghas a relevant role in immune response regulation. The overall structure of theHLA-Gcoding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functionalHLA-Gproperties. TheHLA-Gpromoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γand NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influenceHLA-Gexpression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. TheHLA-Gcoding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of theHLA-Gpromoter region and its implication in transcriptional gene control, the structure of theHLA-G3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.

scholarly journals GC- and E-box Motifs as Regulatory Elements in the Proximal Promoter Region of the Neuronal Nicotinic Receptor α7 Subunit Gene

1998 ◽  
Vol 273 (32) ◽  
pp. 20021-20028 ◽  
Author(s):  
Carmen Carrasco-Serrano ◽  
Antonio Campos-Caro ◽  
Salvador Viniegra ◽  
Juan J. Ballesta ◽  
Manuel Criado
Keyword(s):  
Nicotinic Receptor ◽  
Promoter Region ◽  
Regulatory Elements ◽  
Proximal Promoter ◽  
Subunit Gene ◽  
Proximal Promoter Region ◽  
Neuronal Nicotinic Receptor ◽  
E Box ◽  
Α7 Subunit

Polymorphisms in the goat β-lactoglobulin gene

2005 ◽  
Vol 72 (3) ◽  
pp. 379-384 ◽  
Author(s):  
Maria Ballester ◽  
Armand Sánchez ◽  
Josep M Folch
Keyword(s):  
Genetic Variants ◽  
Promoter Region ◽  
Point Mutations ◽  
Proximal Promoter ◽  
Coding Region ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Β Lactoglobulin ◽  
Pyrosequencing Technology ◽  
Frequent Haplotype

β-lactoglobulin polymorphisms have been reported in the milk of different goat breeds, although no genetic variants affecting the protein have been characterized. In the present study, we amplified and sequenced the proximal promoter and the first six exons containing the entire coding region for the β-lactoglobulin gene in eleven goat breeds from Spain, France, Italy, Switzerland, Senegal and Asia to identify genetic variants. Fifteen polymorphisms were detected, nine in the promoter region and six in the exons of the β-lactoglobulin gene. All polymorphisms were single nucleotide substitutions with the exception of one deletion/insertion in the promoter region. The polymorphisms in the coding region did not produce any amino acid change. In addition, pyrosequencing technology was used to genotype four polymorphisms in the promoter region in 200 goats belonging to eleven breeds. Differences in allelic frequencies for these polymorphisms between breeds are described and a specific polymorphism for the Italian populations was identified. Finally, the analysis of association between these four promoter point mutations was investigated resulting in five haplotypes, GCGC being the most frequent haplotype in all breeds analysed.

scholarly journals CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells

Blood ◽  
2012 ◽  
Vol 120 (17) ◽  
pp. 3455-3465 ◽  
Author(s):  
Niklas K. Björkström ◽  
Vivien Béziat ◽  
Frank Cichocki ◽  
Lisa L. Liu ◽  
Jeffrey Levine ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cell Function ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Proximal Promoter ◽  
Differentiated Cells ◽  
High Resolution Analysis ◽  
Autoimmune Conditions

Abstract Epistatic interactions between killer cell immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands have important implications for reproductive success, antiviral immunity, susceptibility to autoimmune conditions and cancer, as well as for graft-versus-leukemia reactions in settings of allogeneic stem cell transplantation. Although CD8 T cells are known to acquire KIRs when maturing from naive to terminally differentiated cells, little information is available about the constitution of KIR repertoires on human CD8 T cells. Here, we have performed a high-resolution analysis of KIR expression on CD8 T cells. The results show that most CD8 T cells possess a restricted KIR expression pattern, often dominated by a single activating or inhibitory KIR. Furthermore, the expression of KIR, and its modulation of CD8 T-cell function, was independent of expression of self-HLA class I ligands. Finally, despite similarities in the stochastic regulation of KIRs by the bidirectional proximal promoter, the specificity of inhibitory KIRs on CD8 T cells was often distinct from that of natural killer cells in the same individual. The results provide new insight into the formation of KIR repertoires on human T cells.

Three new HLA class I alleles with synonymous mutations: HLA-A*03:01:62 , -C*07:02:82 and -C*12:03:42

HLA ◽  
2017 ◽  
Vol 91 (1) ◽  
pp. 60-61 ◽  
Author(s):  
M. R. Moya-Quiles ◽  
A. Balas ◽  
M. Muro ◽  
A. M. García-Alonso ◽  
J. L. Vicario
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Synonymous Mutations

scholarly journals Mutational Analysis of the Uukuniemi Virus (Bunyaviridae Family) Promoter Reveals Two Elements of Functional Importance

2002 ◽  
Vol 76 (21) ◽  
pp. 10849-10860 ◽  
Author(s):  
Ramon Flick ◽  
Fredrik Elgh ◽  
Ralf F. Pettersson
Keyword(s):  
Rna Polymerase ◽  
Promoter Region ◽  
Mutational Analysis ◽  
Single Point ◽  
Proximal Promoter ◽  
Coding Region ◽  
Base Pairing ◽  
Viral Polymerase ◽  
Proximal Promoter Region ◽  
Pol I

ABSTRACT We have performed an extensive mutational analysis of the proposed promoter region of the phlebovirus Uukuniemi (UUK), a member of the Bunyaviridae family. This was achieved by using a recently developed RNA polymerase I (Pol I)-driven reverse genetics system (R. Flick and R. F. Pettersson, J. Virol. 75:1643-1655, 2001). Chimeric cDNAs containing the coding region for the reporter chloramphenicol acetyltransferase (CAT) in an antisense orientation were flanked by the 5′- and 3′-terminal nontranslated regions of the UUK virus-sense RNA (vRNA) derived from the medium-sized (M) RNA segment. The chimeric cDNAs (Pol I expression cassettes) were cloned between the murine Pol I promoter and terminator, and the plasmids were transfected into BHK-21 cells. CAT activity was determined after cotransfection with viral expression plasmids encoding the RNA-dependent RNA polymerase (L) and the nucleoprotein (N) or, alternatively, after superinfection with UUK virus helper virus. Using oligonucleotide-directed mutagenesis, single point mutations (substitutions, deletions, and insertions) were introduced into the viral promoter region. Differences in CAT activities were interpreted to reflect the efficiency of mRNA transcription from the mutated promoter and the influence on RNA replication. Analysis of 109 mutants allowed us to define two important regulatory regions within the proximal promoter region (site A, positions 3 to 5 and 2 to 4; site B, positions 8 and 8, where underlined nucleotides refer to positions in the vRNA 3′ end). Complementary double nucleotide exchanges in the proximal promoter region, which maintained the possibility for base pairing between the 5′ and 3′ ends, demonstrated that nucleotides in the two described regions are essential for viral polymerase recognition in a base-specific manner. Thus, mere preservation of panhandle base pairing between the 5′ and 3′ ends is not sufficient for promoter activity. In conclusion, we have been able to demonstrate that both ends of the M RNA segment build up the promoter region and are involved in the specific recognition by the viral polymerase.

scholarly journals HLA-G: Facts and Fictions

2018 ◽  
Vol 3 (2) ◽  
pp. 37-45
Author(s):  
Parisa Khodabandeh Shahraki ◽  
Ali Alavian-Mehr ◽  
Shirin Farjadian
Keyword(s):  
Cancer Progression ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Serum Levels ◽  
Class I ◽  
Coding Region ◽  
Hla Class I Molecules ◽  
Mhc Class I Molecule ◽  
Potential Biomarker ◽  
Soluble Hla

Human leukocyte antigen (HLA)-G is a nonclassical MHC class I molecule with modulatory effects on NK and T cells. Unlike classical HLA class I molecules, HLA-G has seven isoforms, three of which are soluble. Soluble HLA-G molecules are reportedly able to transduce negative signals to immune cells after interacting with their corresponding receptors. The expression of these molecules plays significant roles in maternal tolerance against semi-allogenic fetuses. Overexpression of HLA-G in tumors and increased serum levels of soluble HLA-G have been reported in different malignancies, and these changes may be involved in tumoral immune evasion and cancer progression. To improve immune responses against tumor cells, the downmodulation of HLA-G by siRNA or blocking monoclonal antibodies can be helpful in cancer immunotherapy. Additionally, HLA-G can be considered a potential biomarker for the diagnosis and/or prognosis of certain cancers. Although polymorphism of the HLA-G gene-coding region is more limited than in classical HLA class I, some genetic variations in regulatory regions of the gene control the expression level of this molecule. Furthermore, epigenetic factors such as infections may affect the expression of HLA-G in infection-related cancers.

Building a metal-responsive promoter with synthetic regulatory elements

1985 ◽  
Vol 5 (6) ◽  
pp. 1480-1489
Author(s):  
P F Searle ◽  
G W Stuart ◽  
R D Palmiter
Keyword(s):  
Thymidine Kinase ◽  
Promoter Region ◽  
Fusion Gene ◽  
Regulatory Elements ◽  
Regulatory Sequence ◽  
Thymidine Kinase Gene ◽  
Coding Region ◽  
Base Pairs ◽  
Promoter Elements ◽  
Kinase Gene

A fusion gene consisting of the promoter region from the mouse metallothionein-I gene joined to the coding region of the herpes simplex virus thymidine kinase gene is efficiently regulated by zinc in a transient assay when transfected into baby hamster kidney cells. Analysis of similar plasmids in which the metallothionein-I promoter region was mutated indicated the presence of multiple metal regulatory elements (MREs) between -176 and -44 base pairs from the cap site. To further investigate the function of MREs, we inserted a synthetic DNA fragment containing the sequence of MRE-a (the element between -55 and -44 base pairs) into the nonresponsive promoter of the thymidine kinase gene in various positions and configurations. Little or no induction by zinc was observed with single insertions of the regulatory sequence, whereas many different constructions having two copies of MRE-a were inducible. The precise position of the two MREs relative to each other or to the thymidine kinase promoter elements had a relatively small effect on the efficiency of induction, but the inducibility could be further increased by the introduction of more MRE-a sequences. MRE-a can function synergistically with the thymidine kinase distal promoter elements, but in the presence of the TATA box alone it functions as a positive, zinc-dependent promoter element.

Sign in / Sign up

Export Citation Format

Share Document