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Analysis of the effect of two IgH superenhancer deletion on IgH locus transcription

ABSTRACT: Analysis of the effect of two IgH superenhancer deletion on IgH locus transcription

OTHER RELATED OMICS DATASETS IN: GSE90760GSE90758

PROVIDER: PRJNA355859 | ENA |

REPOSITORIES: ENA

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Analysis of the effect of two IgH superenhancer deletion on IgH locus transcription

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-13 | GSE90760 | GEO

Effects of the HDACi SAHA on IgH transcription in B-cell splenocytes and effect of deletion of two cis-transcriptional enhancer on IgH transcription in femoral B-cells.

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

HDAC inhibitors and IgH locus transcription. Mini 3'RR and IgH locus transcription

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

Altered 3D chromatin structure permits inversional recombination at the IgH locus

Project description:We report that in the absence of intergenic control region 1 (IGCR1), a regulatory sequence that specifies the RAG scanning domain on WT IgH alleles, VH and DH gene segments can recombine with each other by both deletion and inversion of intervening DNA.

2020-07-02 | GSE135763 | GEO

Altered 3D chromatin structure permits inversional recombination at the IgH locus

2020-06-18 | GSE133185 | GEO

Two modes of cis-activation of switch transcription by the IgH superenhancer.

Project description:B cell isotype switching plays an important role in modulating adaptive immune responses. It occurs in response to specific signals that often induce different isotype (I) promoters driving transcription of switch regions, located upstream of the Ig heavy chain (IgH) constant genes. The transcribed switch regions can recombine, leading to a change of the constant gene and, consequently, of antibody isotype. Switch transcription is controlled by the superenhancer 3' regulatory region (3'RR) that establishes long-range chromatin cis-interactions with I promoters. Most stimuli induce more than one I promoter, and switch transcription can occur on both chromosomes. Therefore, it is presently unknown whether induced I promoters compete for the 3'RR on the same chromosome. Here we performed single-chromosome RT-qPCR assays to examine switch transcription monoallelically in the endogenous context. We show that there are two modes of 3'RR-mediated activation of I promoters: coactivation and competition. The nature of the inducing signal plays a pivotal role in determining the mode of activation. Furthermore, we provide evidence that, in its endogenous setting, the 3'RR has a bidirectional activity. We propose that the coactivation and competition modes mediated by the 3'RR may have evolved to cope with the different kinetics of primary immune responses.

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The superenhancer binding factor Med1 is broadly required for optimally expressing and hypermutating IgH genes as well as for terminating their expression through locus suicide recombination

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

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Project description:We reoprt that in the absence of intergenic control region 1 (IGCR1), a regulatory sequence that specifies the RAG scanning domain on WT IgH alleles, VH and DH gene segments can recombine with each other by both deletion and inversion of intervening DNA.

2020-07-01 | GSE145472 | GEO

HDAC inhibitors and IgH locus transcription. Mini 3'RR and IgH locus transcription

Project description:HDAC inhibitors and IgH locus transcription. Mini 3'RR and IgH locus transcription

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Effects of the HDACi SAHA on IgH transcription in B-cell splenocytes and effect of deletion of two cis-transcriptional enhancer on IgH transcription in femoral B-cells.

Project description:Effects of the HDACi SAHA on IgH transcription in B-cell splenocytes and effect of deletion of two cis-transcriptional enhancer on IgH transcription in femoral B-cells.

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