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GSE35554
Mus musculus, Drosophila melanogaster, Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina Genome Analyzer II
Description
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD. Overall design: The RNA sequencing libraries were constructed from the liver RNA of 3-4-month Smarcal1del/del and wt female mice (n=3/group) at 20°C and after 1 hour at 39.5°C. These libraries were sequenced using the whole transcriptome shotgun sequencing procedure.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila, and mouse models, we show that the proteins encoded by SMARCAL1 orthologues localize to transcriptionally active chromatin and modulate gene expression. We also show that similar to SIOD patients, deficiency of the SMARCAL1 orthologues alone is insufficient to cause disease in fruit flies and mice although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
Publication Title
Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in SWI/SNF-related matrix associated actin-dependent regulator of chromatin, subfamily A-like protein 1 (SMARCAL1). Changes in gene expression appear to underlie the immunodeficiency and arteriosclerosis of SIOD; therefore, we hypothesized that SMARCAL1 deficiency alters renal gene expression to cause the focal segmental glomerulosclerosis (FSGS) of SIOD, and that these gene expression alterations would be comparable to those observed in isolated FSGS. We tested this hypothesis by gene expression microarray analysis.
Publication Title
Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in SWI/SNF-related matrix associated actin-dependent regulator of chromatin, subfamily A-like protein 1 (SMARCAL1). Changes in gene expression appear to underlie the immunodeficiency and arteriosclerosis of SIOD; therefore, we hypothesized that SMARCAL1 deficiency alters renal gene expression to cause the focal segmental glomerulosclerosis (FSGS) of SIOD. We tested this hypothesis by transcriptome analysis and quantitative reverse transcription PCR (qRT-PCR) of an SIOD patient kidney, a genetic screen and immunofluorescence. These showed increased expression of genes in the Wnt and Notch signaling pathways in an SIOD patient kidney, interaction of Marcal1 with genes encoding components of the Wnt and Notch signaling pathways, and increased levels of unphosphorylated b-catenin and Notch1 intracellular domain (NICD) in the glomeruli of SIOD patient kidneys. Given that increased Wnt and Notch activity are established causes of FSGS, we hypothesize that SMARCAL1 deficiency increases the activity of one or both of these pathways to cause the renal disease of most SIOD patients. Overall design: Comparison of mRNA levels between the kidney tissue of a Schimke immuno-osseous dysplasia (SIOD) patient and an unaffected control
Publication Title
Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acids-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acids uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acids metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.
Publication Title
Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.
Publication Title
Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Malat1 is not an essential component of nuclear speckles in mice.
Sample Metadata Fields
Age, Specimen part
View Samples