POEMS syndrome Immunoglobulin sequences
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB35157 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR3664750_1.fastq.gz | Fastqsanger.gz | |||
| ERR3664750_2.fastq.gz | Fastqsanger.gz | |||
| ERR3664760_1.fastq.gz | Fastqsanger.gz | |||
| ERR3664760_2.fastq.gz | Fastqsanger.gz |
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Project description:Somatic hypermutation (SHM) drives the genetic diversity of immunoglobulin genes in activated B cells and supports the generation of antibodies with increased affinity for antigen. SHM is targeted to Ig genes by their enhancers (DIVACs; diversification activators) but how the enhancers mediate this activity is unknown. We show that DIVACs that strongly stimulate SHM increase the phosphorylation of RNA polymerase 2 (Pol2) and Pol2 occupancy in the mutating gene with little or no accompanying increase in elongation-competent Pol2 or production of full length transcripts, indicating the accumulation of stalled Pol2. DIVAC-induced stalling is weakly associated with an increase in the detection of single-stranded DNA bubbles in the mutating target gene. We did not find evidence for anti-sense transcription or an association of H3K27ac with DIVAC activity in the mutating gene. These findings argue for a connection between Pol2 stalling and cis-acting targeting elements in the context of SHM and thus define a mechanistic basis for locus-specific targeting of SHM in the genome. Our results suggest that DIVACs make the target gene a suitable platform for AID-mediated mutation without the need for increasing transcriptional output.
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