Mus musculus strain:C57BL/6J
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1124255 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29481704_1.fastq.gz | Fastqsanger.gz | |||
| SRR29481704_2.fastq.gz | Fastqsanger.gz | |||
| SRR29481714_1.fastq.gz | Fastqsanger.gz | |||
| SRR29481714_2.fastq.gz | Fastqsanger.gz | |||
| SRR29481675_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:In adaptive immunity, transcription-coupled damage is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID-damage, ELOF1 mechanistically facilitates both transcription-coupled damage and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.
2025-03-01 | GSE284306 | GEO
Project description:In adaptive immunity, transcription-coupled damage is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID-damage, ELOF1 mechanistically facilitates both transcription-coupled damage and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.
2025-03-01 | GSE284305 | GEO
Project description:In adaptive immunity, transcription-coupled damage is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID-damage, ELOF1 mechanistically facilitates both transcription-coupled damage and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.
2025-03-01 | GSE284303 | GEO
Project description:Programmed mutagenesis of the immunoglobulin locus of B-lymphocytes during class switch recombination and somatic hypermutation requires RNA polymerase II (RNA polII) transcription complex dependent targeting of the DNA mutator, Activation Induced cytidine Deaminase (AID). AID deaminates cytidine residues on substrate sequences in the immunoglobulin (Ig) locus via a transcription-dependent mechanism and this activity is stimulated by the RNA polII stalling co-factor Spt5 and the eleven-subunit cellular non-coding RNA 3’-5’ exonucleolytic processing complex, RNA exosome. The mechanism by which the RNA exosome recognizes immunoglobulin locus RNA substrates to stimulate AID DNA deamination activity on its in vivo substrate sequences is an important question. Here we report that E3-ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII by a ubiquitination event leading to generation of 3’-end free RNA exosome RNA substrates at the Ig locus and other AID target sequences genome-wide. Using highthrough-out RNA sequencing technology, we find that lack of Nedd4 activity in B cells leads to accumulation of RNA exosome substrates at AID target genes. Moreover, we find that Nedd4-deficient B cells are inefficient in undergoing class switch recombination. Taken together, our study links non-coding RNA processing following RNA polymerase II pausing with regulation of the mutator AID protein. Our study also identifies Nedd4 as a regulator of non-coding RNA that are generated by stalled RNA polII genome-wide. Splenic B cells from Nedd4+/+ and Nedd4-/- B cells fetal liver chimeric mice were were stimulated in culture for IgG1 CSR. Total RNA was isolated and evaluated with whole genome RNA-seq
2013-08-07 | E-GEOD-49027 | biostudies-arrayexpress
Project description:Programmed mutagenesis of the immunoglobulin locus of B-lymphocytes during class switch recombination and somatic hypermutation requires RNA polymerase II (RNA polII) transcription complex dependent targeting of the DNA mutator, Activation Induced cytidine Deaminase (AID). AID deaminates cytidine residues on substrate sequences in the immunoglobulin (Ig) locus via a transcription-dependent mechanism and this activity is stimulated by the RNA polII stalling co-factor Spt5 and the eleven-subunit cellular non-coding RNA 3’-5’ exonucleolytic processing complex, RNA exosome. The mechanism by which the RNA exosome recognizes immunoglobulin locus RNA substrates to stimulate AID DNA deamination activity on its in vivo substrate sequences is an important question. Here we report that E3-ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII by a ubiquitination event leading to generation of 3’-end free RNA exosome RNA substrates at the Ig locus and other AID target sequences genome-wide. Using highthrough-out RNA sequencing technology, we find that lack of Nedd4 activity in B cells leads to accumulation of RNA exosome substrates at AID target genes. Moreover, we find that Nedd4-deficient B cells are inefficient in undergoing class switch recombination. Taken together, our study links non-coding RNA processing following RNA polymerase II pausing with regulation of the mutator AID protein. Our study also identifies Nedd4 as a regulator of non-coding RNA that are generated by stalled RNA polII genome-wide.
2013-08-07 | GSE49027 | GEO
Project description:MYC family proteins are oncogenic transcription factors that can globally affect the function of RNA Polymerase II (RNAPII). The ability of MYC proteins to promote transcription elongation depends on their ubiquitination, but the underlying mechanism and its biological relevance are unknown. Here we show that MYC and the Polymerase II associated factor, PAF1c, interact directly and their function is mutually dependent, since the specific binding of MYC to active promoters depends on PAF1c and, conversely, PAF1c is required for MYC-dependent pause release. Upon binding, PAF1c is rapidly transferred from MYC onto RNAPII and this transfer is driven by the HUWE1 ubiquitin ligase. Both MYC and HUWE1 globally control histone H2B ubiquitylation, which promotes transcriptional elongation and alters chromatin structure for double-strand break repair. Consistently, MYC suppresses the accumulation of double-strand breaks at promoters in response to topoisomerase II inhibition. While depletion of PAF1c has only minor effects on MYC-dependent gene expression, MYC induces rampant transcription-dependent DNA damage in PAF1c-depleted cells. We propose that the HUWE1-dependent transfer of PAF1c from MYC onto RNAPII is critical for absorbing the topological stress accompanied with deregulated and oncogenic transcription.
2021-02-15 | PXD023242 | Pride
Project description:Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA Polymerase II (Pol II), causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions (TBLs). However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR/cas9 screen, we identified elongation factor ELOF1 as an important new factor in the transcription stress response upon DNA damage. We show that ELOF1 has an evolutionary conserved role in Transcription-Coupled Nucleotide Excision Repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair TBLs and resume transcription. Additionally, ELOF1 modulates transcription to protect cells from transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms.
2021-04-20 | PXD025304 | Pride
Project description:The prevalence of some autoimmune diseases (AID) is greater in females compared with males, notwithstanding that disease severity is often greater in males. The reason for this sexual dimorphism (SD) is unknown, but may reflect negative selection of Y chromosome (ChrY) bearing sperm during spermatogenesis or male fetuses early in the course of conception/pregnancy. Previously, we showed that the SD in experimental autoimmune encephalomyelitis (EAE) is associated with copy number variation (CNV) in ChrY multicopy genes. Here, we test the hypothesis that CNV in ChrY multicopy genes influences the paternal parent-of-origin effect on EAE susceptibility in female mice. We show that C57BL/6J consomic strains of mice possessing an identical ChrX and CNV in ChrY multicopy genes exhibit a female biased sex-ratio and sperm head abnormalities, consistent with X-Y intragenomic conflict arising from an imbalance in CNV between homologous ChrX:ChrY multicopy genes. These males also display paternal transmission of EAE to female offspring and differential loading of miRNAs within the sperm nucleus. These findings provide evidence for a genetic mechanism at the level of the male gamete that contributes to the SD in EAE and paternal parent-of-origin effects in female mice, raising the possibility that a similar mechanism may contribute to the SD in MS.
2015-01-16 | GSE65047 | GEO
Project description:The prevalence of some autoimmune diseases (AID) is greater in females compared with males, notwithstanding that disease severity is often greater in males. The reason for this sexual dimorphism (SD) is unknown, but may reflect negative selection of Y chromosome (ChrY) bearing sperm during spermatogenesis or male fetuses early in the course of conception/pregnancy. Previously, we showed that the SD in experimental autoimmune encephalomyelitis (EAE) is associated with copy number variation (CNV) in ChrY multicopy genes. Here, we test the hypothesis that CNV in ChrY multicopy genes influences the paternal parent-of-origin effect on EAE susceptibility in female mice. We show that C57BL/6J consomic strains of mice possessing an identical ChrX and CNV in ChrY multicopy genes exhibit a female biased sex-ratio and sperm head abnormalities, consistent with X-Y intragenomic conflict arising from an imbalance in CNV between homologous ChrX:ChrY multicopy genes. These males also display paternal transmission of EAE to female offspring and differential loading of miRNAs within the sperm nucleus. These findings provide evidence for a genetic mechanism at the level of the male gamete that contributes to the SD in EAE and paternal parent-of-origin effects in female mice, raising the possibility that a similar mechanism may contribute to the SD in MS. miRNA expression was analyzed in epidydimal sperm pooled from 5 mice for each replicate per strain.
2015-01-16 | E-GEOD-65047 | biostudies-arrayexpress