Possible involvement of the calreticulin gene in the evolution of cognition in humans

2011 ◽  
Vol 26 (S2) ◽  
pp. 810-810
Author(s):  
T. Farokhashtiani ◽  
A. Mirabzadeh ◽  
M. Ohadi
Keyword(s):  
Schizoaffective Disorder ◽  
Core Promoter ◽  
Promoter Sequence ◽  
Type I ◽  
Specific Expression ◽  
The Core ◽  
Human Promoter ◽  
Genetic Overlap ◽  
Higher Order Functions ◽  
The Brain

The chromosomal region, 19p 13.2, has been suggested to be linked with schizoaffective disorder (Hamshere et al. 2005). This region harbors the calreticulin gene, protein encoded by which is an endoplasmic Ca+2-binding molecular chaperone. Development-dependent, tissue-specific expression of this gene in the gray matter coincides with the expression of psychoses phenotypes. We have recently reported instances of mutations within the core promoter (−48 G>C, −205 C>T) and coding sequence [exon 5 (c: 682 C>T, pro228ser)] of the gene in schizoaffective disorder. In view of the mounting evidence on the genetic overlap in the psychiatric spectrum, we investigated this gene in 386 patients afflicted with schizophrenia, schizoaffective disorder, major affective disorder and 600 controls by PCR/SSCA. We found that a unique mutation within the core promoter of the gene, located at a conserved genomic block, co-occurring with four cases of psychoses including schizophrenia, schizoaffective disorder and bipolar disorder type I. This unique mutation reverts the human promoter sequence to the ancestral types observed in chimpanzee, rhesus Macaque and mouse, implying that the genomic block harboring this nucleotide may be involved in the evolution of human-specific higher-order functions of the brain (i.e. cognition), that are ubiquitously impaired in psychoses. Our findings propose that calreticulin is not only a promising candidate in the spectrum of psychoses, but also, a gene that may be important in the process of human-unique higher-level functions of the brain.

scholarly journals Hepatocyte-specific expression of the hepatitis B virus core promoter depends on both positive and negative regulation.

1993 ◽  
Vol 13 (1) ◽  
pp. 443-448 ◽  
Author(s):  
W Guo ◽  
M Chen ◽  
T S Yen ◽  
J H Ou
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mammalian Cells ◽  
Core Promoter ◽  
Regulatory Sequence ◽  
Cell Type Specificity ◽  
Specific Expression ◽  
The Core ◽  
Upstream Regulatory Sequence ◽  
B Virus

The core promoter of hepatitis B virus shows hepatocyte specificity, which is largely dependent on an upstream regulatory sequence that overlaps with viral enhancer II. Footprint analyses by numerous groups have shown binding by cellular proteins over a large stretch of DNA in this region, but the identity of these proteins and their role in core promoter function remain largely unknown. We present data showing that the transcription factor HNF-4 is one such factor, as it activates the core promoter approximately 20-fold via a binding site within the upstream regulatory sequence. Since HNF-4 is enriched in hepatocytes, its involvement at least partially explains the hepatocyte specificity of this promoter. In addition, however, we have found a region upstream of the HNF-4 site that suppresses activation by HNF-4 in HeLa cells but not in hepatoma cells. Therefore, the cell type specificity of the core promoter appears to result from a combination of activation by one or more factors specifically enriched in hepatocytes and repression by some other factor(s) present in nonhepatocytes, and it may provide a convenient model system for studying this type of tissue-specific transcriptional regulation in mammalian cells.

scholarly journals Methylation in the Core-promoter Region of the Chondromodulin-I Gene Determines the Cell-specific Expression by Regulating the Binding of Transcriptional Activator Sp3

2004 ◽  
Vol 279 (27) ◽  
pp. 28789-28797 ◽  
Author(s):  
Tomoki Aoyama ◽  
Takeshi Okamoto ◽  
Satoshi Nagayama ◽  
Koichi Nishijo ◽  
Tatsuya Ishibe ◽  
...  
Keyword(s):  
Promoter Region ◽  
Core Promoter ◽  
Transcriptional Activator ◽  
Core Promoter Region ◽  
Specific Expression ◽  
The Core ◽  
I Gene

Core promoter-selective RNA polymerase II transcription

2006 ◽  
Vol 73 ◽  
pp. 225-236 ◽  
Author(s):  
Petra Gross ◽  
Thomas Oelgeschläger
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Core Promoter ◽  
Promoter Sequence ◽  
Tata Box ◽  
Promoter Elements ◽  
The Core ◽  
Core Promoter Sequence ◽  
Rnap Ii

The initiation of mRNA synthesis in eukaryotic cells is a complex and highly regulated process that requires the assembly of general transcription factors and RNAP II (RNA polymerase II; also abbreviated as Pol II) into a pre-initiation complex at the core promoter. The core promoter is defined as the minimal DNA region that is sufficient to direct low levels of activator-independent (basal) transcription by RNAP II in vitro. The core promoter typically extends approx. 40 bp up- and down-stream of the start site of transcription and can contain several distinct core promoter sequence elements. Core promoters in higher eukaryotes are highly diverse in structure, and each core promoter sequence element is only found in a subset of genes. So far, only TATA box and INR (initiator) element have been shown to be capable of directing accurate RNAP II transcription initiation independent of other core promoter elements. Computational analysis of metazoan genomes suggests that the prevalence of the TATA box has been overestimated in the past and that the majority of human genes are TATA-less. While TATA-mediated transcription initiation has been studied in great detail and is very well understood, very little is known about the factors and mechanisms involved in the function of the INR and other core promoter elements. Here we summarize our current understanding of the factors and mechanisms involved in core promoter-selective transcription and discuss possible pathways through which diversity in core promoter architecture might contribute to combinatorial gene regulation in metazoan cells.

scholarly journals Regulation of Pdha-2 expression is mediated by proximal promoter sequences and CpG methylation.

1997 ◽  
Vol 17 (2) ◽  
pp. 612-619 ◽  
Author(s):  
R C Iannello ◽  
J Young ◽  
S Sumarsono ◽  
M J Tymms ◽  
H H Dahl ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Promoter Activity ◽  
Core Promoter ◽  
Pyruvate Dehydrogenase Complex ◽  
Cpg Methylation ◽  
Proximal Promoter ◽  
Specific Gene ◽  
Specific Expression ◽  
Cpg Dinucleotides ◽  
The Core

Spermatogenesis is a complex process requiring the coordinate expression of a number of testis-specific genes. One of these, Pdha-2, codes for the murine spermatogenesis-specific isoform of the E1a subunit of the pyruvate dehydrogenase complex. To begin to delineate the mechanisms regulating its expression in vivo, we have generated transgenic mice lines carrying Pdha-2 promoter deletion constructs. Here we report that transgenic mice harboring a construct containing only 187 bp of promoter and upstream sequences (core promoter) is sufficient for directing the testis-specific expression of a chloramphenicol acetyltransferase (CAT) reporter gene. Like the endogenous Pdha-2, the CAT gene is expressed in testis in a stage-specific manner. Our studies also show a correlation between CpG methylation within the core promoter and its capacity to regulate transcription. In NIH 3T3 cell lines stably transfected with the Pdha-2 core promoter-CAT construct, high levels of CAT reporter expression are observed, whereas the endogenous Pdha-2 gene is repressed. In these cells, the CpG dinucleotides residing within the transfected promoter are hypomethylated whereas those residing in the endogenous promoter are methylated. Furthermore, promoter activity can be abated by the in vitro methylation of its CpG dinucleotides. DNase I footprint analysis indicates that at least one site for the methylation-mediated repression may occur through the ATF/cyclic AMP response element binding element located within the core promoter. Mutations within this element reduces activity to approximately 50% of the wild-type promoter activity. These results suggest that tissue-specific gene expression may be modulated by other mechanisms in addition to specific transcription factor availability and cooperativity. We propose that methylation may be a mechanism by which repression of the testis-specific Pdha-2 gene is established in somatic tissue.

SPAN-XB Core Promoter Sequence Is Regulated in Myeloma Cells by Specific CpG Dinucleotides Associated with MeCP2 Protein.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2216-2216
Author(s):  
Zhiqing Wang ◽  
Jian Zhang ◽  
Yana Zhang ◽  
Kalkunte Srivenugopal ◽  
Seah H. Lim
Keyword(s):  
Gene Expression ◽  
Core Promoter ◽  
Promoter Sequence ◽  
Base Pairs ◽  
Myeloma Cells ◽  
Cpg Dinucleotides ◽  
The Core ◽  
Core Sequence ◽  
Promoter Gene ◽  
Protein Mecp2

Abstract SPAN-Xb is a spermatid-specific protein encoded by the SPAN-XB gene on chromosome Xq27.1. It is a novel Cancer-Testis antigen in multiple myeloma. We recently demonstrated that SPAN-Xb expression in myeloma cells is regulated through promoter methylation and could be upregulated by IL-7 and GM-CSF. In this present study, we set out to investigate the mechanism of SPAN-XB expression and the promoter association with the methyl-CpG binding protein, MeCP2. Elucidation of these interactions is likely to shed light on potential therapeutic strategies to upregulate antigen levels that could be used to improve the outcome of SPAN-Xb-based tumor vaccines. We previously showed that the putative SPAN-XB promoter resides within exon 1 and contains 433 bp, starting from position −546 to position −104 upstream of the translational start site. Using a panel of truncated promoter constructs generated from the 3′ and 5′ ends of the promoter gene, we localized the core sequence of SPAN-XB promoter to the 73 base pairs at the 3-end of the promoter, a region that lacks CpG dinucleotides within the full length promoter. There are 11 CpG dinucleotides within the putative SPAN-XB promoter. We previously found that DNA methylation provides the primary regulatory mechanism for SPAN-XB gene expression. We also identified that hypomethylation at positions −310, −307, −299 and −221 strongly predicted for SPAN-XB expression, suggesting the involvement of these four CpG dinucleotides in the regulation of SPAN-XB gene expression through DNA methylation. In the present study, using reporter gene expression assays, we found that the core promoter function is significantly modulated by these adjacent CpG sequences so that mutation of the CpG dinucleotides outside the core sequence resulted in changes in the promoter function. We also previously demonstrated by bisulfite conversion and sequence analysis the association between methylation at specific CpG dinucleotides with repression of SPAN-XB gene. Here, we extended our study to determine whether or not the methylated cytosine binding protein, MeCP2, interacts with the SPAN-XB promoter gene in myeloma cells. Chromatin immunoprecipitation assays revealed a specific association of the MeCP2 with SPAN-XB promoter, and MeCP2 binding strongly correlated with repression of the SPAN-XB gene in myeloma cell lines and CD138-enriched fresh myeloma cells. Reactivation of the SPAN-XB gene by 5-azacytidine treatment resulted in the loss of MeCP2 from this site. We, therefore, conclude that SPAN-XB promoter consists of a core sequence and a regulatory element; the core element resides within the 73 base pairs at the 3′ end of the full length promoter. SPAN-XB gene expression by the core sequence is regulated in myeloma cells by specific CpG nucleotides and associated with MeCP2 binding to the promoter sequence.

Hepatocyte-specific expression of the hepatitis B virus core promoter depends on both positive and negative regulation

1993 ◽  
Vol 13 (1) ◽  
pp. 443-448
Author(s):  
W Guo ◽  
M Chen ◽  
T S Yen ◽  
J H Ou
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mammalian Cells ◽  
Core Promoter ◽  
Regulatory Sequence ◽  
Cell Type Specificity ◽  
Specific Expression ◽  
The Core ◽  
Upstream Regulatory Sequence ◽  
B Virus

The core promoter of hepatitis B virus shows hepatocyte specificity, which is largely dependent on an upstream regulatory sequence that overlaps with viral enhancer II. Footprint analyses by numerous groups have shown binding by cellular proteins over a large stretch of DNA in this region, but the identity of these proteins and their role in core promoter function remain largely unknown. We present data showing that the transcription factor HNF-4 is one such factor, as it activates the core promoter approximately 20-fold via a binding site within the upstream regulatory sequence. Since HNF-4 is enriched in hepatocytes, its involvement at least partially explains the hepatocyte specificity of this promoter. In addition, however, we have found a region upstream of the HNF-4 site that suppresses activation by HNF-4 in HeLa cells but not in hepatoma cells. Therefore, the cell type specificity of the core promoter appears to result from a combination of activation by one or more factors specifically enriched in hepatocytes and repression by some other factor(s) present in nonhepatocytes, and it may provide a convenient model system for studying this type of tissue-specific transcriptional regulation in mammalian cells.

The Core of What the Brain Does

PsycCRITIQUES ◽  
2017 ◽  
Vol 62 (44) ◽  
Author(s):  
David S. Kreiner
Keyword(s):  
The Core ◽  
The Brain

Macroscopic Anatomy and Brain Vascularization in the Greater Rhea (Rhea americana americana)

2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Herson Da Silva Costa ◽  
Hélio Norberto De Araújo Júnior ◽  
Ferdinando Vinícius Fernandes Bezerra ◽  
Carlos Eduardo Vale Rebouças ◽  
Danilo José Ayres De Menezes ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Carotid Arteries ◽  
Vascular System ◽  
Cerebral Arteries ◽  
Cervical Region ◽  
Type I ◽  
Macroscopic Anatomy ◽  
Rhea Americana ◽  
Vascular Type ◽  
The Brain

 Background: The Rhea americana americana is a wild bird belonging to the group of Ratites, and is important from the scientific point of view given their adaptability to captivity. Considering that information about its morphology is important for the viability of domesticating the species, the aim of this study was to macroscopically identify the brain regions, as well as the cerebral arteries and the cerebral arterial circuit in order to establish the cerebral vascular pattern and systematization.Materials, Methods & Results: Twenty one brains from young and adult Greater Rheas of both sexes were used from animals that had died due to natural causes and were then kept in a freezer. The specimens were thawed and incised in the cervical region to allow exposure of the left common carotid artery, which was cannulated. The vascular system was rinsed with 0.9% saline solution, then perfused with latex Neoprene 650 stained with red pigment. The animals were subsequently fixed in 3.7% aqueous formaldehyde solution for 72 h, and then they were dissected by removing the bones from the skull cap. The brains were analyzed, and the structures were identified, photographed, schematized and denominated. Morphometric measurements were performed on the basilar and cerebellar ventral caudal arteries, recording the values of length and width in millimeters with the aid of a digital caliper. The brain was divided into: telencephalon, diencephalon, brainstem and cerebellum; while externally, the observed structures are: olfactory bulbs, optical lobes, optic nerves, optic chiasm, pituitary and pineal glands. Vascularization was performed by the following arteries: ventral spinal artery, basilar artery, ventricular cerebellar arteries, medium ventricular cerebellar arteries, caudal branches of the carotid arteries of the brain, ventral mesencephalic artery, cerebral caudal arteries, rostral branches of the carotid arteries of the brain, middle cerebral arteries, cerebroethmoidal arteries, rostral intercerebral anastomosis, rostral cerebral arteries, ethmoidal arteries, internal ophthalmic arteries, inter-hemispheric artery, pituitary arteries, dorsal mesencephalic tectal arteries, dorsal cerebellar arteries, occipital, pineal and dorsal hemispherical branches. The cerebral arterial circuit was both caudally and rostrally closed in 100.0% of the samples, being composed of the arteries: basilar artery, caudal branches of the carotid brain, rostral branches of the brain carotid, cerebroethmoidal arteries and rostral intercerebral anastomosis.Discussion: Encephalon classification regarding the presence or absence of gyri is a characteristic associated to evolution­ary aspects among vertebrates, being respectively considered as lisencephalon or girencecephalus when it presents or does not present convolutions. In Greater Rheas, the telencephalon was quite developed, with a relatively rounded shape and the absence of sulci and convolutions in the cortex, which allowed it to be classified as a lisencephalon. Such findings resemble those described for the ostrich and in a comparative study involving kiwis, emus, owls and pigeons, although different sizes and forms of telencephalon development were observed in the latter. Regarding the cerebral arterial circuit, this structure in Rheas was complete and both caudally and rostrally closed in 100.0% of the specimens. Our findings differ from those ob­served for ostriches, in which a rostrally open behavior has been described, while it is caudally closed in 20.0% of cases and opened in 80.0%. Regarding the vascular type of the brain, in the Rhea it was observed that there was only contribution of the carotid system, similar to that found for birds such as ostriches and turkeys which confer a type I encephalic vascularization.Keywords: arteries, brain, arterial circuit, morphometry, ratites.

scholarly journals A 1232 bp upstream sequence of glutamine synthetase 1b from Eichhornia crassipes is a root-preferential promoter sequence

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanshan Zhong ◽  
Xiaodan Lu ◽  
Zhiwei Deng ◽  
Ziqing Lu ◽  
Minghui Fu
Keyword(s):  
Glutamine Synthetase ◽  
Eichhornia Crassipes ◽  
Invasive Plant ◽  
Promoter Sequence ◽  
Regulatory Mechanisms ◽  
Pcr Analysis ◽  
Regulation Mechanism ◽  
Upstream Sequence ◽  
Specific Expression ◽  
N Metabolism

Abstract Background Glutamine synthetase (GS) acts as a key enzyme in plant nitrogen (N) metabolism. It is important to understand the regulation of GS expression in plant. Promoters can initiate the transcription of its downstream gene. Eichhornia crassipes is a most prominent aquatic invasive plant, which has negative effects on environment and economic development. It also can be used in the bioremediation of pollutants present in water and the production of feeding and energy fuel. So identification and characterization of GS promoter in E. crassipes can help to elucidate its regulation mechanism of GS expression and further to control its N metabolism. Results A 1232 bp genomic fragment upstream of EcGS1b sequence from E. crassipes (EcGS1b-P) has been cloned, analyzed and functionally characterized. TSSP-TCM software and PlantCARE analysis showed a TATA-box core element, a CAAT-box, root specific expression element, light regulation elements including chs-CMA1a, Box I, and Sp1 and other cis-acting elements in the sequence. Three 5′-deletion fragments of EcGS1b upstream sequence with 400 bp, 600 bp and 900 bp length and the 1232 bp fragment were used to drive the expression of β-glucuronidase (GUS) in tobacco. The quantitative test revealed that GUS activity decreased with the decreasing of the promoter length, which indicated that there were no negative regulated elements in the EcGS1-P. The GUS expressions of EcGS1b-P in roots were significantly higher than those in leaves and stems, indicating EcGS1b-P to be a root-preferential promoter. Real-time Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis of EcGS1b gene also showed higher expression in the roots of E.crassipes than in stems and leaves. Conclusions EcGS1b-P is a root-preferential promoter sequence. It can specifically drive the transcription of its downstream gene in root. This study will help to elucidate the regulatory mechanisms of EcGS1b tissue-specific expression and further study its other regulatory mechanisms in order to utilize E.crassipes in remediation of eutrophic water and control its overgrowth from the point of nutrient metabolism.

scholarly journals Investigation of the Wilson gene ATP7B transcriptional start site and the effect of core promoter alterations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clemens Höflich ◽  
Angela Brieger ◽  
Stefan Zeuzem ◽  
Guido Plotz
Keyword(s):  
Wilson Disease ◽  
Transcription Initiation ◽  
Transcriptional Activity ◽  
Core Promoter ◽  
Transcriptional Start Site ◽  
Copper Metabolism ◽  
Biologically Relevant ◽  
The Core ◽  
Translational Start

AbstractPathogenic genetic variants in the ATP7B gene cause Wilson disease, a recessive disorder of copper metabolism showing a significant variability in clinical phenotype. Promoter mutations have been rarely reported, and controversial data exist on the site of transcription initiation (the core promoter). We quantitatively investigated transcription initiation and found it to be located in immediate proximity of the translational start. The effects human single-nucleotide alterations of conserved bases in the core promoter on transcriptional activity were moderate, explaining why clearly pathogenic mutations within the core promoter have not been reported. Furthermore, the core promoter contains two frequent polymorphisms (rs148013251 and rs2277448) that could contribute to phenotypical variability in Wilson disease patients with incompletely inactivating mutations. However, neither polymorphism significantly modulated ATP7B expression in vitro, nor were copper household parameters in healthy probands affected. In summary, the investigations allowed to determine the biologically relevant site of ATP7B transcription initiation and demonstrated that genetic variations in this site, although being the focus of transcriptional activity, do not contribute significantly to Wilson disease pathogenesis.

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