Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome wide profiling of RNA Pol II and CSB in CS1AN cells or wild type CSB reconstituted cells [ChIP-seq]

ABSTRACT: We report how CSB affects globally the density of RNA Pol II at TSS and how this effect correlates with the gene expression alterations observed from microarray analysis. We also show globally the distribution of CSB. RNA Pol II and CSB ChIP-Seq in CS1AN cells and CSB reconstituted wild type cells, in duplicate, using Illumina GAIIx

ORGANISM(S): Homo sapiens

SUBMITTER: Yuming Wang

PROVIDER: E-GEOD-58253 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease.

Wang Yuming Y Chakravarty Probir P Ranes Michael M Kelly Gavin G Brooks Philip J PJ Neilan Edward E Stewart Aengus A Schiavo Giampietro G Svejstrup Jesper Q JQ

Proceedings of the National Academy of Sciences of the United States of America 20140923 40

Cockayne syndrome (CS) is a multisystem disorder with severe neurological symptoms. The majority of CS patients carry mutations in Cockayne syndrome group B (CSB), best known for its role in transcription-coupled nucleotide excision repair. Indeed, because various repair pathways are compromised in patient cells, CS is widely considered a genome instability syndrome. Here, we investigate the connection between the neuropathology of CS and dysregulation of gene expression. Transcriptome analysis ...[more]

PMID: 25249633

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Project description:Cockayne syndrome is an inherited premature aging syndrome associated with developmental and neurological disorders. Mutations in the genomic locus encoding CSB are associated with 80% Cockayne syndrome cases. Transcription profiling assays reveal the association of mis-regulation of gene expression with Cockayne syndrome, highlighting the importance of CSB in transcription regulation. However, many questions remain unanswered as how CSB regulates transcription. In this study, we dissect the mechanisms by which CSB regulates transcription during normal growth. By anti-CSB chromatin immunoprecipitation followed by deep sequencing, we found CSB is enriched at genomic regions containing TGASTCA motifs, to which the immediate early gene product C-Jun binds specifically. We further demonstrate that c-Jun co-immunoprecipitates with CSB. In addition, the targeting of CSB to genomic region containing TGASTCA motifs was drastically reduced in cells treated c-Jun shRNA. Reverse transcription followed by quantitative PCR indicates that CSB can regulate gene expression nearby its binding sites, both in activation and repression. The remodeling defective CSBM-bM-^HM-^FN1 mutant is also targeted to TGASTCA motifs, but cannot always substitute CSB function in transcription regulating, suggesting the importance of remodeling by CSB in transcription regulation. Notably, the Cockayne syndrome related mutation encoding protein CSBR670W, which is defective in ATP hydrolysis but is targeted to TGASTCA motifs efficiently, indicating that ATP hydrolysis is dispensable for c-Jun mediated CSB targeting, in sharp contrast to the ATP-dependent targeting mechanism by which CSB is relocated to DNA lesion stalled transcription. Together, these results reveal a second CSB targeting mechanism in which DNA sequence specific transcription factor c-Jun targets CSB to specific genomic region and regulate gene expression. Genomic localization of CSB and remodeling deficient CSBM-bM-^HM-^FN1

Dataset Information

Genome wide profiling of RNA Pol II and CSB in CS1AN cells or wild type CSB reconstituted cells [ChIP-seq]

Publications

Dysregulation of gene expression as a cause of Cockayne syndrome neurological disease.

Similar Datasets

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