Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A gene expression fingerprint in mental retardation reflects disease causing defects in the histone demethylase KDM5

ABSTRACT: Mutations in KDM5C, (previously named SMCX or JARID1C) a gene that encodes a transcriptional regulator with histone-demethylase activity specific for di- and tri-methylated H3K4, are a comparatively frequent cause of non-syndromic X-linked mental retardation (NS-XLMR). Specific transcriptional targets of KDM5C, however, are still unknown and the effects of KDM5C deficiency on gene expression have not yet been investigated. Here we present the results of gene expression profiling performed on lymphoblastoid cell lines as well as blood from patients with mutations in KDM5C. Using whole genome expression arrays and QRT-PCR we identified several genes, including CMKOR1, JARID1B and KIAA0469 that were consistently deregulated in both tissues. These findings shed light on the patho-mechanisms underlying mental retardation and may have implications for future diagnostics of this heterogeneous disorder. We compared the mRNA expression of a patient lymphoblastoid cell line deficient for KDM5C with that of three controls to identify genes that are deregulated in the patient cell line.

ORGANISM(S): Homo sapiens

SUBMITTER: Lars Jensen

PROVIDER: E-GEOD-17369 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

A gene expression fingerprint in mental retardation reflects disease causing defects in the histone demethylase KDM5

Project description:Mutations in KDM5C, (previously named SMCX or JARID1C) a gene that encodes a transcriptional regulator with histone-demethylase activity specific for di- and tri-methylated H3K4, are a comparatively frequent cause of non-syndromic X-linked mental retardation (NS-XLMR). Specific transcriptional targets of KDM5C, however, are still unknown and the effects of KDM5C deficiency on gene expression have not yet been investigated. Here we present the results of gene expression profiling performed on lymphoblastoid cell lines as well as blood from patients with mutations in KDM5C. Using whole genome expression arrays and QRT-PCR we identified several genes, including CMKOR1, JARID1B and KIAA0469 that were consistently deregulated in both tissues. These findings shed light on the patho-mechanisms underlying mental retardation and may have implications for future diagnostics of this heterogeneous disorder.

2009-07-29 | GSE17369 | GEO

NO001: Kdm5c controls promoter and enhancer activities

Project description:The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes like enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in embryonic stem cells and neuronal progenitor cells via gene-specific transcription factors. Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our data show that restricting H3K4me3 modification at core promoters dampens transcription, but Kdm5c is required at enhancers for their full activity. Remarkably, an impaired enhancer function activates the intrinsic promoter activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c demethylase plays a crucial and dynamic role in the functional discrimination between enhancers and core promoters. RNA from four independent cultures from each sh Kdm5c #1, sh Kdm5c #2 and non-targeting shRNA polyclonal cell lines were hybridized in dye-swap against a common reference of RNA from IB10 ES cells.

2013-04-05 | E-GEOD-38862 | biostudies-arrayexpress

Activation of Xist by An Evolutionarily Conserved Function of the KDM5C Demethylase

Project description:We performed Kdm5c (Smcx) ChIP-Seq in del_Tsix XY mouse epiblast cells with two genotypes: Smcx-WT and Smcx-KO

2022-04-14 | GSE96740 | GEO

NO001: Kdm5c controls promoter and enhancer activities

2013-04-05 | GSE38862 | GEO

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (ChIP-seq)

Project description:Transcriptional dysregulation is an early feature of Huntington's disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD.

2013-07-18 | GSE48960 | GEO

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (RNA-seq)

2013-07-18 | GSE48962 | GEO

Loss of histone demethylase JARID1C triggers genomic instability in cancer.

Project description:Chromatin remodelers are recurrently mutated in cancer. Among these, JARID1C, (KDM5C) a histone demethylase, is frequently inactivated in clear cell renal cell carcinoma (ccRCC) patients. How the genetic inactivation of JARID1C leads to cancer remains largely unknown. Here we report that JARID1C binds to broad chromatin domains characterized by the trimethylation of lysine 9 (H3K9me3), an histone mark enriched in heterochromatin. We also found that JARID1C localizes on heterochromatin, is required for heterochromatin replication, and forms a complex with established and novel players of heterochromatin assembly, such as SUV39H1 and HP1 and the CUL4 complex adaptor protein DDB1, respectively. To safeguard the genome, transcription on heterochromatin is tightly suppressed. JARID1C inactivation leads to the unrestrained expression of heterochromatic ncRNAs, that in turn trigger genomic instability. Remarkably, ccRCC patients harbouring JARID1C mutations show aberrant ncRNA expression and increased genomic rearrangements when compared with tumors endowed with other genetic lesions. Together, these data suggest that the inactivation of JARID1C in renal cancer leads to heterochromatin disruption and to aggressive, genomically rearranged ccRCCs, shedding light on a novel mechanism underlying genomic instability in sporadic cancers. We performed ChIP-sequencing for KDM5C, H3K9me3, H3K4me1 and H3K4me3 in Caki-1 untreated cells. Platform HiSeq2500.

2015-11-09 | E-GEOD-73267 | biostudies-arrayexpress

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (RNA-seq)

2013-07-18 | E-GEOD-48962 | biostudies-arrayexpress

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (ChIP-seq)

2013-07-18 | E-GEOD-48960 | biostudies-arrayexpress