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Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vk Gene Rearrangement in Pre-B Cells and Pro-B Cells [VDJ-seq]

ABSTRACT: Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vk Gene Rearrangement in Pre-B Cells and Pro-B Cells [VDJ-seq]

PROVIDER: PRJNA483208 | ENA |

REPOSITORIES: ENA

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Epigenetic enhancer marks and transcription factor binding influence Vk gene rearrangement frequencies in pre-B cells and pro-B cells

Project description:Deep sequencing has the potential to provide great insight into the composition of the antibody repertoire and is now widely used. To date there has not been a study directly comparing relative rearrangement frequencies obtained with unbiased amplification from genomic DNA (gDNA) and cDNA from the same set of cells to elucidate any differences. Here we use a recently developed method for unbiased amplification of gDNA and directly compare the data to the unbiased RNA IgK repertoire from the same pre-B cell pool. We find that ~20% of Vk genes have relative rearrangement frequencies > 2-fold up or down in the RNA vs DNA libraries, including many members of the Vk4, Vk3 and Vk6 families. Regression analysis indicates that Ikaros and E2A binding are associated with strong promoters. Within the pre-B repertoire, we found that the vastly unequal Vk gene rearrangement frequencies are best predicted by epigenetic marks of enhancers. In particular, the levels of newly arising H3K4me1 peaks associated with many Vk genes in pre-B cells are most predictive of rearrangement levels. Comparison of IgK rearrangements that occur in pro-B cells and pre-B cells from the same mice reveal a pro-B cell bias towards usage of Jk-distal Vk genes, particularly Vk 10-96 and surrounding genes. Regression analysis indicates that PU.1 binding is the highest predictor of high Vk gene rearrangement frequency in pro-B cells. Lastly, repertoires of iEk -/- pre-B cells reveal that the intronic enhancer actively influences Vk gene usage and displays a germline transcriptional sphere of influence extending to Vk 6-15, overlapping with the deficit in Jk proximal Vk gene usage. These represent previously unknown roles for iEk in addition to its major function in stimulating overall IgK rearrangement.

2018-10-01 | GSE113306 | GEO

Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vk Gene Rearrangement in Pre-B Cells and Pro-B Cells [VDJ-seq]

Project description:There has been no study to date that has examined genomic DNA (gDNA) and RNA Igkappa repertoires directly from the same set of cells. In this study we performed deep sequencing on Igkappa repertoire library preparations from both gDNA and RNA from the same sorted cells. This was done for both pre-B cells, where most Igkappa rearrangement takes places as well as pro-B cells where some B cells undergo early Igkappa rearrangement. In addition, we perfored gDNA repertoire analysis on iEkappa-/- pre-B cells. We find that some Vk genes display skewed DNA or RNA representiation relative to the other. We also find that pro-B cell Igkappa rearrangement is skewed to Jkappa-distal Vkappa genes. Lastly, we find that iEkappa-/- pre-B cells are not capable of rearranging to the most proximal Vkappa family genes.

2018-10-01 | GSE117800 | GEO

Epigenetic enhancer marks and transcription factor binding influence Vk gene rearrangement frequencies in pre-B cells and pro-B cells

Project description:Epigenetic enhancer marks and transcription factor binding influence Vk gene rearrangement frequencies in pre-B cells and pro-B cells

| PRJNA450755 | ENA

Bacillus safensis VK strain:VK

Project description:Bacillus safensis VK strain:VK Genome sequencing and assembly

| PRJNA210810 | ENA

Igh repertoire analysis in primary pro-B cells from WT and NE1-/- mice (VDJ-seq)

Project description:Analysis of the antibody repertoire composition is now possible using VDJ-seq. We used this recently developed method for unbiased amplification from genomic DNA (gDNA) to directly compare the Igh repertoire of C57Bl/6 (WT) and NE1-/- pro-B cells. We find that a group of contiguous proximal and intermediate VH genes are under-utilized in V->DJ rearrangement in the absence of NE1 revealing a NE1 zone of influence. We report the VH gene usage profile from WT and NE1-/- primary pro-B cells from the VDJ-seq data.

2022-12-22 | GSE203484 | GEO

Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vkappa Gene Rearrangement in Pre-B Cells and Pro-B Cells

Project description:Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vkappa Gene Rearrangement in Pre-B Cells and Pro-B Cells

| PRJNA483209 | ENA

Gene expression profile in multiple myeloma tumors from Vk*MYC mice

Project description:Myeloma tumors arose in Vk*MYC mice share gene expression profile with multiple myeloma tumors from human patients

2020-02-20 | GSE111921 | GEO

Evaluation of CNAs in multiple myeloma tumors from Vk*MYC mice

Project description:Myeloma tumors arose in Vk*MYC mice share copy number abnormalities with multiple myeloma tumors from human patients

2020-02-20 | GSE110954 | GEO

Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination

Project description:Background: V(D)J recombination is an essential process for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igk) light chain locus recombination follows recombination of the immunoglobulin heavy chain (Igh) locus. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. In conjunction with genome-wide datasets for several epigenetic features, we showed that two active chromatin states, located at the recombination signal sequences (RSS) of VH genes, are highly predictive of recombination. The contribution of chromatin features to Vk gene choice in recombination remains poorly understood. Results: We adapted the VDJ-seq assay to profile the Igk VkJk repertoire, and obtained a comprehensive readout of highly variable Vk gene usage in mouse bone marrow pre-B cells. We identified PU.1 binding at the RSS as highly predictive of whether a gene will actively recombine or not. Prediction of the frequency of recombination was more dependent on H3K4 methylation and IKAROS binding. Conclusions: Epigenetic features within the Vk region are able to explain much of the variation in Vk gene usage. Whilst PU.1 binding at the RSS appears to play a binary, all-or-nothing role, priming Vk genes for recombination, the frequency with which these genes recombine is shaped by the presence and enrichment of a number of other epigenetic features. In contrast to the Igh locus, the epigenetic landscape of the promoter as well as the RSS is predictive of Vk gene recombination.

2017-11-03 | GSE101606 | GEO

Bacillus safensis strain:VK contig00023

Project description:Bacillus safensis VK contig00023 genome sequencing

| PRJNA334010 | ENA