Search results for "Matrix Attachment Region Binding Proteins"

showing 3 items of 3 documents

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

2021

AbstractWhereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene,SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carryingSATB1variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression…

0301 basic medicineMaleModels MolecularMISSENSE MUTATIONSCHROMATINTranscription GeneticCellMedizinDiseaseHaploinsufficiencymedicine.disease_cause0302 clinical medicineMissense mutationde novo variantsGenetics (clinical)INTERLEUKIN-2seizuresGenetics0303 health sciencesMutationChromatin bindingneurodevelopmental disordersMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]SATB1Phenotypemedicine.anatomical_structureintellectual disabilityFemaleHaploinsufficiencyteeth abnormalitiesProtein BindingNeuroinformaticsEXPRESSIONGENESMutation MissenseBiologyBINDING PROTEINREGION03 medical and health sciencesSATB1Protein DomainsReportGeneticsmedicineHPO-based analysisHumansGenetic Association StudiesHpo-based Analysis ; Satb1 ; Cell-based Functional Assays ; De Novo Variants ; Intellectual Disability ; Neurodevelopmental Disorders ; Seizures ; Teeth Abnormalities030304 developmental biology[SDV.GEN]Life Sciences [q-bio]/GeneticsNeurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]Matrix Attachment Region Binding Proteins030104 developmental biologyNeurodevelopmental DisordersMutationNanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]030217 neurology & neurosurgerycell-based functional assays
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Satb2 Regulates Callosal Projection Neuron Identity in the Developing Cerebral Cortex

2008

SummarySatb2 is a DNA-binding protein that regulates chromatin organization and gene expression. In the developing brain, Satb2 is expressed in cortical neurons that extend axons across the corpus callosum. To assess the role of Satb2 in neurons, we analyzed mice in which the Satb2 locus was disrupted by insertion of a LacZ gene. In mutant mice, β-galactosidase-labeled axons are absent from the corpus callosum and instead descend along the corticospinal tract. Satb2 mutant neurons acquire expression of Ctip2, a transcription factor that is necessary and sufficient for the extension of subcortical projections by cortical neurons. Conversely, ectopic expression of Satb2 in neural stem cells m…

Chromatin ImmunoprecipitationNeuroscience(all)Electrophoretic Mobility Shift AssayMice TransgenicNerve Tissue ProteinsDEVBIOBiologyCorpus callosumMOLNEUROMiceNeural PathwaysmedicineAnimalsCells CulturedCerebral CortexNeuronsRegulation of gene expressionStem CellsGeneral NeuroscienceGene Expression Regulation DevelopmentalMatrix Attachment Region Binding ProteinsDNAEmbryo MammalianNeural stem cellChromatinmedicine.anatomical_structureAnimals NewbornBromodeoxyuridinenervous systemCerebral cortexRegulatory sequenceMutationCorticospinal tractEctopic expressionNeuroscienceTranscription Factors
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The utility of SATB2 immunohistochemical expression in distinguishing between osteosarcomas and their malignant bone tumor mimickers, such as Ewing s…

2016

SATB2 is commonly expressed in osteosarcomas. Although apparently being a valuable diagnostic marker for differentiating between small cell osteosarcoma (SCO) and other small round cell tumors of bone, for instance Ewing sarcoma family of tumors (ESFT), it has not been tested in a large series of ESFT and chondrosarcomas so far. We studied the immunohistochemical expression of SATB2 in 42 osteosarcomas, 31 chondrosarcomas, and 371 genetically confirmed ESFT. SATB2 positivity was detected in 90.4% of osteosarcomas, 87.5% of SCO, 91.3% of osteoblastic osteosarcomas, and in all chondroblastic and parosteal osteosarcomas. The osteoblastic and SCO subtypes expressed SATB2 more intensely than oth…

musculoskeletal diseases0301 basic medicinePathologymedicine.medical_specialtyCD99ChondrosarcomaBone NeoplasmsSarcoma EwingSensitivity and SpecificitySmall Cell OsteosarcomaPathology and Forensic MedicineDiagnosis Differential03 medical and health sciences0302 clinical medicineChondroblastic OsteosarcomaBiomarkers TumormedicineHumansRetrospective StudiesOsteosarcomabusiness.industryOsteoidMatrix Attachment Region Binding ProteinsCell Biologymusculoskeletal systemmedicine.diseaseImmunohistochemistry030104 developmental biology030220 oncology & carcinogenesisImmunohistochemistryOsteosarcomaSarcomaChondrosarcomabusinessTranscription FactorsPathology - Research and Practice
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