scholarly journals Transcriptional inhibition of the murine erythropoietin receptor gene by an upstream repetitive element.

1993 ◽  
Vol 13 (1) ◽  
pp. 98-104 ◽  
Author(s):  
H Youssoufian ◽  
H F Lodish
Keyword(s):  
Reporter Gene ◽  
Mouse Genome ◽  
Repetitive Element ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Erythropoietin Receptor ◽  
Erythroid Cells ◽  
Rnase Protection ◽  
Transcriptional Inhibition ◽  
Sense Orientation

Transcription of the murine erythropoietin receptor (EpoR) gene is inhibited by a novel repetitive element that is located upstream of the EpoR promoter. Reporter gene studies reveal that the inhibitory effect is both distance and orientation dependent. This element is a member of a family of repetitive elements specific to rodents and is present at approximately 10(5) copies per mouse genome. It encodes approximately 500- to 900-bp-long transcripts in both erythroid and nonerythroid cells. RNase protection analysis with a probe from the 5' flanking murine EpoR gene reveals that the direction of transcription is in the sense orientation, relative to the downstream EpoR gene. We suggest that transcriptional inhibition of the EpoR promoter is mediated by read-through transcripts originating in the upstream repetitive element and that this effect may contribute to the basal level of transcription of the murine EpoR gene in erythroid cells.

Transcriptional inhibition of the murine erythropoietin receptor gene by an upstream repetitive element

1993 ◽  
Vol 13 (1) ◽  
pp. 98-104
Author(s):  
H Youssoufian ◽  
H F Lodish
Keyword(s):  
Reporter Gene ◽  
Mouse Genome ◽  
Repetitive Element ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Erythropoietin Receptor ◽  
Erythroid Cells ◽  
Rnase Protection ◽  
Transcriptional Inhibition ◽  
Sense Orientation

Transcription of the murine erythropoietin receptor (EpoR) gene is inhibited by a novel repetitive element that is located upstream of the EpoR promoter. Reporter gene studies reveal that the inhibitory effect is both distance and orientation dependent. This element is a member of a family of repetitive elements specific to rodents and is present at approximately 10(5) copies per mouse genome. It encodes approximately 500- to 900-bp-long transcripts in both erythroid and nonerythroid cells. RNase protection analysis with a probe from the 5' flanking murine EpoR gene reveals that the direction of transcription is in the sense orientation, relative to the downstream EpoR gene. We suggest that transcriptional inhibition of the EpoR promoter is mediated by read-through transcripts originating in the upstream repetitive element and that this effect may contribute to the basal level of transcription of the murine EpoR gene in erythroid cells.

scholarly journals Genetic Background of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1151
Author(s):  
Mary Frances McMullin
Keyword(s):  
Receptor Gene ◽  
Cell Mass ◽  
Oxygen Affinity ◽  
Young Age ◽  
Erythropoietin Receptor ◽  
Congenital Defects ◽  
History Of ◽  
Genetic Mechanisms ◽  
High Oxygen Affinity ◽  
Hemoglobin Variants

True erythrocytosis is present when the red cell mass is greater than 125% of predicted sex and body mass, which is reflected by elevated hemoglobin and hematocrit. Erythrocytosis can be primary or secondary and congenital or acquired. Congenital defects are often found in those diagnosed at a young age and with a family history of erythrocytosis. Primary congenital defects mainly include mutations in the Erythropoietin receptor gene but SH2B3 has also been implicated. Secondary congenital erythrocytosis can arise through a variety of genetic mechanisms, including mutations in the genes in the oxygen sensing pathway, with high oxygen affinity hemoglobin variants and mutations in other genes such as BPMG, where ultimately the production of erythropoietin is increased, resulting in erythrocytosis. Recently, mutations in PIEZ01 have been associated with erythrocytosis. In many cases, a genetic variant cannot be identified, leaving a group of patients with the label idiopathic erythrocytosis who should be the subject of future investigations. The clinical course in congenital erythrocytosis is hard to evaluate as these are rare cases. However, some of these patients may well present at a young age and with sometimes catastrophic thromboembolic events. There is little evidence to guide the management of congenital erythrocytosis but the use of venesection and low dose aspirin should be considered.

Lyn kinase plays important roles in erythroid expansion, maturation and erythropoietin receptor signalling by regulating inhibitory signalling pathways that control survival

2014 ◽  
Vol 459 (3) ◽  
pp. 455-466 ◽  
Author(s):  
Neli S. Slavova-Azmanova ◽  
Nicole Kucera ◽  
Alison Louw ◽  
Jiulia Satiaputra ◽  
Adley Handoko ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cell Development ◽  
Erythropoietin Receptor ◽  
Erythroid Cell ◽  
Signalling Pathways ◽  
Erythroid Cells ◽  
Src Family Kinase ◽  
Receptor Signalling ◽  
Lyn Kinase ◽  
Control Survival

In erythroid cells both positive viability signals and feedback inhibitory signalling require the Src family kinase Lyn, influencing cell survival and their ability to differentiate. This illustrates that Lyn is critical for normal erythropoiesis and erythroid cell development.

Activation and inhibition of erythropoietin receptor function: role of receptor dimerization

1994 ◽  
Vol 14 (6) ◽  
pp. 3535-3549
Author(s):  
S S Watowich ◽  
D J Hilton ◽  
H F Lodish
Keyword(s):  
Signal Transduction ◽  
Growth Hormone Receptor ◽  
Initial Step ◽  
Inhibitory Effect ◽  
Erythropoietin Receptor ◽  
Interface Region ◽  
Wild Type ◽  
Receptor Dimerization ◽  
Dimer Interface ◽  
Constitutively Active

Members of the cytokine receptor superfamily have structurally similar extracellular ligand-binding domains yet diverse cytoplasmic regions lacking any obvious catalytic domains. Many of these receptors form ligand-induced oligomers which are likely to participate in transmembrane signaling. A constitutively active (factor-independent) mutant of the erythropoietin receptor (EPO-R), R129C in the exoplasmic domain, forms disulfide-linked homodimers, suggesting that the wild-type EPO-R is activated by ligand-induced homodimerization. Here, we have taken two approaches to probe the role EPO-R dimerization plays in signal transduction. First, on the basis of the crystal structure of the ligand-bound, homodimeric growth hormone receptor (GH-R) and sequence alignment between the GH-R and EPO-R, we identified residues of the EPO-R which may be involved in intersubunit contacts in an EPO-R homodimer. Residue 129 of the EPO-R corresponds to a residue localized to the GH-R dimer interface region. Alanine or cysteine substitutions were introduced at four other residues of the EPO-R predicted to be in the dimer interface region. Substitution of residue E-132 or E-133 with cysteine renders the EPO-R constitutively active. Like the arginine-to-cysteine mutation at position 129 in the exoplasmic domain (R129C), E132C and E133C form disulfide-linked homodimers, suggesting that constitutive activity is due to covalent dimerization. In the second approach, we have coexpressed the wild-type EPO-R with inactive mutants of the receptor missing all or part of the cytosolic domain. These truncated receptors have a dominant inhibitory effect on the proliferative action of the wild-type receptor. Taken together, these results strengthen the hypothesis that an initial step in EPO- and EPO-R-mediated signal transduction is ligand-induced receptor dimerization.

Genomic organization of the human erythropoietin receptor gene

Genomics ◽  
1991 ◽  
Vol 11 (4) ◽  
pp. 974-980 ◽  
Author(s):  
Laura A. Penny ◽  
Bernard G. Forget
Keyword(s):  
Genomic Organization ◽  
Receptor Gene ◽  
Erythropoietin Receptor ◽  
Human Erythropoietin

scholarly journals Inhibitory Effect of Epstein-Barr Virus Gene-Ebna1 on Human Tnfrp55 Gene Expression

2012 ◽  
Vol 56 (3) ◽  
pp. 271-274
Author(s):  
Joanna Krzowska-Firych ◽  
Hanna Fota-Markowska ◽  
Barbara Marzec-Kotarska ◽  
Roma Modrzewska ◽  
Jacek Wojcierowski
Keyword(s):  
Gene Expression ◽  
Epstein Barr Virus ◽  
Human Peripheral Blood ◽  
Rnase Protection Assay ◽  
Inhibitory Effect ◽  
Gene Encoding ◽  
Rnase Protection ◽  
Barr Virus ◽  
Epstein Barr ◽  
Ebna1 Gene

Abstract The aim of the study was to assess the expression of TNFRp55 mRNA and to examine if the antisense inhibition of Epstein-Barr virus (EBV) encoded EBNA1 gene product alters the expression of gene encoding TNFRp55 in lymphoblastoid cell line (LCL). The experiment was performed on LCL derived from EBV infected human peripheral blood B lymphocytes. The lymphocytes were isolated and cultured. RNA was isolated and examined according to the RNase protection assay. The hybridisation was done with HCR-4 probe. RNA was quantified by densitometry and presented in extinction units. The level of expression was calculated with TotaILab software programme. The results of the study suggest that EBV gene, responsible for the synthesis of EBNA1 protein, has an inhibitory effect on human TNFRp55 gene expression in LCL.

Abstract 255: The Kidney and Heart are Hemogenic Organs During Embryonic Life.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Yan Hu ◽  
Minghong Li ◽  
R. Ariel Gomez ◽  
Maria Luisa S Sequeira Lopez
Keyword(s):  
General Circulation ◽  
Heart Function ◽  
Erythropoietin Receptor ◽  
Erythroid Cells ◽  
Scientific Controversy ◽  
Hematopoietic Stem ◽  
Adult Mice ◽  
Circulating Cells ◽  
Receptor Locus ◽  
Embryonic Life

During early embryonic life, the heart starts to beat before an effective circulation is established, and the kidney starts to form its vasculature before it connects to the general circulation. We and others have shown a close lineage relationship between endothelial cells (ECs) and hematopoietic cells. In fact, during embryonic development erythroblasts bud from the endothelium of developing vessels, a process we termed hemovasculogenesis. Those studies suggested the possibility that embryonic organs may have hemogenic potential. To test this hypothesis, we performed lineage studies and colony forming unit (CFC) assays to trace the fate of hematopoietic stem cells (HSCs), erythroid cells, and ECs in heart and kidney from embryonic mice. Using ER-GFPcre mice that express both GFP and cre under control of the erythropoietin receptor locus in the erythroid cells, we identified hematopoietic progenitors (Hb+Nanog+) within nascent vessels in the early embryonic kidney and heart. Using EC-SCL-Cre-ERT transgenic mice that specifically express tamoxifen inducible Cre in EC progenitors, we found both circulating and non-circulating cells from the EC lineage in the early embryonic heart and kidney. CFC assays using HSC-SCL-Cre-ERT; mTmG mice (which express GFP in the cells from the HSC lineage upon tamoxifen induction) showed that both the embryonic kidney and heart possess HSCs. Further, transplantation studies of pre-vascular embryonic kidneys from EC-SCL-Cre-ERT;R26R mice under the kidney capsule of WT adult mice showed blood cells derived from the embryonic kidney suggesting that the embryonic kidney also possesses HSCs that originate in situ. These studies indicate that the embryonic kidney and heart function as hematopoietic organs during early embryogenesis. In addition to solve an important scientific controversy in our understanding of lineage/fate relationships in the developing embryo, these findings are relevant for tissue repair/regeneration and may help explain why under pathological circumstances, hematopoiesis occurs in extramedullary organs.

Urea inhibits hypertonicity-inducible TonEBP expression and action

2001 ◽  
Vol 280 (5) ◽  
pp. F904-F912 ◽  
Author(s):  
Wei Tian ◽  
David M. Cohen
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanism ◽  
Reporter Gene ◽  
Gene Transcription ◽  
Phorbol Ester ◽  
Renal Medulla ◽  
Inhibitory Effect ◽  
Characteristic Set ◽  
Enhancer Element ◽  
Enhancer Binding Protein

Tonicity-responsive genes are regulated by the TonE enhancer element and the tonicity-responsive enhancer binding protein (TonEBP) transcription factor with which it interacts. Urea, a permeant solute coexistent with hypertonic NaCl in the mammalian renal medulla, activates a characteristic set of signaling events that may serve to counteract the effects of NaCl in some contexts. Urea inhibited the ability of hypertonic stressors to increase expression of TonEBP mRNA and also inhibited tonicity-inducible TonE-dependent reporter gene activity. The permeant solute glycerol failed to reproduce these effects, as did cell activators including peptide mitogens and phorbol ester. The inhibitory effect of urea was evident as late as 2 h after the application of hypertonicity. Pharmacological inhibitors of known urea-inducible signaling pathways failed to abolish the inhibitory effect of urea. TonEBP action is incompletely understood, but evidence supports a role for proteasome function and p38 action in regulation; urea failed to inhibit proteasome function or p38 signaling in response to hypertonicity. Consistent with its effect on TonEBP expression and action, urea pretreatment inhibited the effect of hypertonicity on expression of the physiological effector gene, aldose reductase. Taken together, these data 1) define a molecular mechanism of urea-mediated inhibition of tonicity-dependent signaling, and 2) underscore a role for TonEBP abundance in regulating TonE-mediated gene transcription.

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