Analysis of the effect of two IgH superenhancer deletion on IgH locus transcription
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ABSTRACT:
PROVIDER: PRJNA355859 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5068730_1.fastq.gz | Fastqsanger.gz | |||
| SRR5068730_2.fastq.gz | Fastqsanger.gz | |||
| SRR5068740.fastq.gz | Fastqsanger.gz | |||
| SRR5068731_1.fastq.gz | Fastqsanger.gz | |||
| SRR5068731_2.fastq.gz | Fastqsanger.gz |
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Project description:B-cell development is spatially and temporally regulated with the Ig heavy chain (IgH) locus as a conductor. Starting with the first steps of B-cell development, IgH DNA remodeling constantly occurs under the control of several cis-regulatory elements scattered all along the IgH locus. Their individual genomic deletion had partial or no effect on B-cell development. In this study we investigate the effect of the dual deletion of 5’Eµ and 3’RR enhancer on IgH transcription. Numerous B-cell lymphomas feature translocations linking oncogenes with the IgH locus and epigenetic drugs such as histone deacetylase inhibitors (HDACi) have been approved to treat some of them. In this study we investigated IgH locus transcription in B-cell splenocytes stimùulated with LPS and the HDACi SAHA.
2021-03-27 | GSE169691 | GEO
Project description:Numerous B-cell lymphomas feature translocations linking oncogenes with the IgH locus and epigenetic drugs such as histone deacetylase inhibitors (HDACi) have been approved to treat some of them. In this study we investigated IgH locus transcription in B-cell splenocytes stimulated with LPS and the HDACi SAHA. B-cell development is spatially and temporally regulated with the 3'RR enhancer of the IgH locus as a conductor. 3'RR is composed of 4 enhancer elements with a palindromic structure of great significance. We investigated the role of this palindrome with KOKI mice where the 30Kb structure of the 3'RR has been deleted of its palindromic structure.
2021-03-27 | GSE169690 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-13 | GSE90760 | GEO
Project description:HDAC inhibitors and IgH locus transcription. Mini 3'RR and IgH locus transcription
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Project description:Non-coding sense and antisense germline transcription within the immunoglobulin heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germline transcription throughout the Igh locus has been done. Therefore, we performed directional RNAseq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two PAIR elements in the distal IghV region. Importantly, long-distance loops measured by 3C are observed between these two active PAIR promoters and EM-NM-<, the start site of IM-NM-< germline transcription, in a lineage- and stage-specific manner, even though this antisense transcription is EM-NM-<-independent. YY1-/- pro-B cells are greatly impaired in distal VH gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-EM-NM-< interactions. ChIP-seq shows high level YY1 binding only at EM-NM-<, but low levels near some antisense promoters. PAIR-EM-NM-< interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal VH genes close to the DJH rearrangement, which is adjacent to EM-NM-<. Therefore, we hypothesize that one key role of non-coding germline transcription is to facilitate locus compaction, allowing distal VH genes to undergo efficient rearrangement. ChIP Seq YY1 vs. input control
2012-10-18 | E-GEOD-40822 | biostudies-arrayexpress
Project description:Non-coding sense and antisense germline transcription within the immunoglobulin heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germline transcription throughout the Igh locus has been done. Therefore, we performed directional RNAseq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two PAIR elements in the distal IghV region. Importantly, long-distance loops measured by 3C are observed between these two active PAIR promoters and Eμ, the start site of Iμ germline transcription, in a lineage- and stage-specific manner, even though this antisense transcription is Eμ-independent. YY1-/- pro-B cells are greatly impaired in distal VH gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-Eμ interactions. ChIP-seq shows high level YY1 binding only at Eμ, but low levels near some antisense promoters. PAIR-Eμ interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal VH genes close to the DJH rearrangement, which is adjacent to Eμ. Therefore, we hypothesize that one key role of non-coding germline transcription is to facilitate locus compaction, allowing distal VH genes to undergo efficient rearrangement. In order to determine the amount and location of sense and antisense non-coding RNA in the Igh locus, we prepared total RNA from CD19+ RAG1-/- pro-B cells. Samples were either pre-enriched in custom Agilent arrays, or directly sequenced. Data from one sample for each condition is included as reflected in the publication.
2012-10-18 | E-GEOD-40984 | biostudies-arrayexpress
Project description:Assembly, expression and maturation of the Immunoglobulin heavy (IgH) chain repertoire necessitates long-range 3D-interactions under regulation by the IgH locus Eµ and 3’ regulatory region (3’RR) super-enhancers. In progenitors, Eµ instrumentally supports VDJ recombination notably towards distal VH genes. In mature cells, the 3’RR first boosts the production of membrane-type IgH transcripts. It later attracts Activation-induced cytidine deaminase at three specific locations: VDJ genes undergoing somatic hypermutation (SHM), switch regions undergoing class switch recombination (CSR), and the 3’RR itself during locus suicide recombination (LSR). In plasma cells devoted to abundant Ig secretion, a late long-range effect is to promote high IgH transcription. The Mediator subunit Med1, which binds super-enhancers and has increased activity after phosphorylation by ERK, was previously attributed a role restricted to class-switched cells. We now show its broader impact on IgH expression, both by promoting recombination of distal VH genes in progenitors and by later supporting SHM. Med1-dependence also marks all long-range functions of the 3’RR, including not only intra- but also trans-chromosomal CSR, LSR, optimal BCR expression and the transcriptional boost featured by plasma cells. Altogether, Med1 appears as a major and specific actor of all the long-range tasks effected by the IgH locus super-enhancers beyond transcription.
2022-10-20 | GSE136845 | GEO
Project description:Non-coding sense and antisense germline transcription within the immunoglobulin heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germline transcription throughout the Igh locus has been done. Therefore, we performed directional RNAseq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two PAIR elements in the distal IghV region. Importantly, long-distance loops measured by 3C are observed between these two active PAIR promoters and Eμ, the start site of Iμ germline transcription, in a lineage- and stage-specific manner, even though this antisense transcription is Eμ-independent. YY1-/- pro-B cells are greatly impaired in distal VH gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-Eμ interactions. ChIP-seq shows high level YY1 binding only at Eμ, but low levels near some antisense promoters. PAIR-Eμ interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal VH genes close to the DJH rearrangement, which is adjacent to Eμ. Therefore, we hypothesize that one key role of non-coding germline transcription is to facilitate locus compaction, allowing distal VH genes to undergo efficient rearrangement.
2012-10-18 | GSE40822 | GEO
Project description:Non-coding sense and antisense germline transcription within the immunoglobulin heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germline transcription throughout the Igh locus has been done. Therefore, we performed directional RNAseq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two PAIR elements in the distal IghV region. Importantly, long-distance loops measured by 3C are observed between these two active PAIR promoters and Eμ, the start site of Iμ germline transcription, in a lineage- and stage-specific manner, even though this antisense transcription is Eμ-independent. YY1-/- pro-B cells are greatly impaired in distal VH gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-Eμ interactions. ChIP-seq shows high level YY1 binding only at Eμ, but low levels near some antisense promoters. PAIR-Eμ interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal VH genes close to the DJH rearrangement, which is adjacent to Eμ. Therefore, we hypothesize that one key role of non-coding germline transcription is to facilitate locus compaction, allowing distal VH genes to undergo efficient rearrangement.
2012-10-18 | GSE40984 | GEO
Project description:These tracks include chromatin interaction data produced using the 5C (chromatin conformation capture carbon copy) method by the Kenter Lab located at the University of Illinois College of Medicine, Chicago, IL. These tracks show looping interactions across the Igh locus using alternating forward and reverse primer design scheme. The 3C method uses formaldehyde crosslinking to covalently associate interacting chromatin segments in intact cells. The cells are then lysed and chromatin is digested with the Hind III restriction enzyme. The digested fragments are ligated under dilute conditions to promote intra-molecular ligation. A genome-wide interaction library of ligation products corresponding to all possible chromatin interactions is produced by this method. In 5C assays, over 12,000 potential ligation products specific to the Igh locus are detected by PCR using multiplexed primer pairs. Here we focused on the 3’ end of the Igh locus to evaluate the status of the constant region domain of the locus in LPS+IL4 activated splenic B cells. We observe that the configuration of the 3’ end of the Igh locus spanning the CH region genes assumes a developmental stage specific configuration in B lineage B cells. We find that the interaction frequency and activation state of the 3’ enhancer increases as B cells mature.
2021-11-23 | GSE183195 | GEO