Objective Orosomucoid-like 3(0RMDL3) has been associated with asthma and a series of autoimmune disorders and is involved in endoplasmic reticulum-mediated inflammatory ***,the clinical significance and molecular mech...
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Objective Orosomucoid-like 3(0RMDL3) has been associated with asthma and a series of autoimmune disorders and is involved in endoplasmic reticulum-mediated inflammatory ***,the clinical significance and molecular mechanism underlying its expression are still largely *** To elucidate the mechanisms in human ORMDL3 transcriptional regulation,we cloned the 1.5-kb genomic DNA fragment containing the putative promoter region and evaluated its transcriptional activity in a luciferase reporter system by deletion analysis. EMSA,CMP,ChIP-Re-ChIP was used to identify the key transcription *** We identified a 68-bp region that functions as a minimal *** analysis predicted that the -64 to -56 bp region contained a signal transducer and activator of transcription 6(STAT6) binding *** mobility shift assay and chromatin immunoprecipitation demonstrated that STAT6 bound to its binding site within the ORMDL3 ***6 overexpression or knockdown could trans-activate or trans-inhibit,respectively,the ORMDL3 promoter containing the STAT6-binding *** 4(IL-4)/IL-13 treatment increased ORMDL3 promoter activity as Well as endogenous ORMDL3 *** and ChIP-Re-ChIP assays revealed that STAT6 and p300 exist in the same protein complex binding to the ORMDL3 *** Our study confirmed that STAT6 plays important roles in regulating the expression of human ORMDL3 by directly binding to the promoter region, which can shed light on a possible role in various human diseases.
INTRODUCTION Hereditary spastic paraplegias(HSPs) are a large heterogeneous group of progressive neurodegenerative diseases characterised by progressive lower extremity weakness and spasticity caused by developmental ...
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INTRODUCTION Hereditary spastic paraplegias(HSPs) are a large heterogeneous group of progressive neurodegenerative diseases characterised by progressive lower extremity weakness and spasticity caused by developmental failure or degeneration of motor axons in the corticospinal *** genetic studies have identified at least 48 genetic loci that are responsible for *** Most of the generationⅢ/Ⅳfamily members were under the onset age and therefore we could not determine whether they were patients or not by phenotype *** family members available for linkage analysis were thus fewer and we were unable to get a high logarithm of odds(LOD) score at *** the available family members, alleles of D2S2347 cosegregated with the *** we could not confirm that SPG4 was the disease gene,we could also not exclude it as a candidate causative gene.D2S2351 had no polymorphism in the *** detected the presence of a mutation in SPG4 in members of the Chinese ADHSP family being studied by Sanger *** results revealed a 14-bp heterozygous deletion(c.1630-1643delTACTCAGGAAGTGA) in exon 15 of SPAST,which led to a frameshift mutation and premature termination of translation(***544profsX28).Our findings were confirmed on identifying that the deletion cosegregated with the phenotype in other affected family *** mutation was absent in 50 normal unaffected individuals who were matched for geographical *** A novel 14-bp heterozygous deletion that induced a frameshift mutation in exon 15 of SPAST(SPG4) was *** mutation was predicted to have functional impact and found to cosegregate with the disease *** Our results have expanded the mutation spectrum of the SPAST *** findings could possibly help clinicians provide prenatal diagnosis of affected foetuses in families where members are known to have such neurodegenerative diseases.
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