Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome binding profile of the conserved CSB-PGBD3 fusion protein in CSB-null UVSS1KO cells

ABSTRACT: The CSB-PGBD3 fusion protein arose over 43 million years ago when a 2.5 kb piggyBac 3 (PGBD3) transposon inserted into intron 5 of the Cockayne syndrome Group B (CSB) gene in the common ancestor of all higher primates. The CSB-PGBD3 fusion protein binds internally-deleted PGBD3 elements called MER85s in vitro, and induces a strong interferon-like innate antiviral immune response when expressed in CSB-null UVSS1KO cells. To explore the connection between DNA binding and gene expression changes induced by CSB-PGBD3, we investigated the genome-wide DNA binding profile of the fusion protein. 1 ChIP sample and 1 unenriched input control from the same crosslinked chromatin pool

ORGANISM(S): Homo sapiens

SUBMITTER: Lucas Gray

PROVIDER: E-GEOD-37919 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tethering of the conserved piggyBac transposase fusion protein CSB-PGBD3 to chromosomal AP-1 proteins regulates expression of nearby genes in humans.

Gray Lucas T LT Fong Kimberly K KK Pavelitz Thomas T Weiner Alan M AM

PLoS genetics 20120927 9

The CSB-PGBD3 fusion protein arose more than 43 million years ago when a 2.5-kb piggyBac 3 (PGBD3) transposon inserted into intron 5 of the Cockayne syndrome Group B (CSB) gene in the common ancestor of all higher primates. As a result, full-length CSB is now coexpressed with an abundant CSB-PGBD3 fusion protein by alternative splicing of CSB exons 1-5 to the PGBD3 transposase. An internal deletion of the piggyBac transposase ORF also gave rise to 889 dispersed, 140-bp MER85 elements that were m ...[more]

PMID: 23028371

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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 binding profile of the conserved CSB-PGBD3 fusion protein in CSB-null UVSS1KO cells

Publications

Tethering of the conserved piggyBac transposase fusion protein CSB-PGBD3 to chromosomal AP-1 proteins regulates expression of nearby genes in humans.

Similar Datasets

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