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Temporal Analyses Reveal a Pivotal Role for Sense and Anti-sense Enhancer RNAs in Coordinate Immunoglobulin Lambda Locus Activation

ABSTRACT: Temporal Analyses Reveal a Pivotal Role for Sense and Anti-sense Enhancer RNAs in Coordinate Immunoglobulin Lambda Locus Activation

PROVIDER: PRJNA1001396 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25496852_1.fastq.gz	Fastqsanger.gz
	SRR25496852_2.fastq.gz	Fastqsanger.gz
	SRR25496853_1.fastq.gz	Fastqsanger.gz
	SRR25496853_2.fastq.gz	Fastqsanger.gz
	SRR25496854_1.fastq.gz	Fastqsanger.gz

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Temporal Analyses Reveal a Pivotal Role for Sense and Anti-sense Enhancer RNAs in Coordinate Immunoglobulin Lambda Locus Activation

Project description:Transcription enhancers are essential activators of V(D)J recombination that orchestrate non-coding transcription through complementary, unrearranged gene segments. How transcription is coordinately increased at spatially distinct promoters, however, remains poorly understood. Using the murine immunoglobulin lambda (Igλ) locus as model, we find that three enhancer-like elements in the 3’ Igλ domain, Eλ3-1, HSCλ1 and HSE-1, show strikingly similar transcription factor binding dynamics and close spatial proximity, suggesting that they form an active enhancer hub. Temporal analyses show coordinate recruitment of complementary V and J gene segments to this hub, with comparable transcription factor binding dynamics to that at enhancers. We find further that E2A, p300, Mediator and Integrator bind to enhancers as early events, whereas YY1 recruitment and eRNA synthesis occur later, corresponding to transcription activation. Remarkably, the interplay between sense and anti-sense enhancer RNA is central to both active enhancer hub formation and coordinate Igλ transcription: Antisense Eλ3-1 eRNA represses Igλ activation whereas temporal analyses demonstrate that accumulating levels of sense eRNA boost YY1 recruitment to stabilise enhancer hub/promoter interactions and lead to coordinate transcription activation. These studies therefore demonstrate for the first time a critical role for threshold levels of sense versus antisense eRNA in locus activation.

2023-08-28 | GSE239925 | GEO

Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation.

Project description:Transcription enhancers are essential activators of V(D)J recombination that orchestrate non-coding transcription through complementary, unrearranged gene segments. How transcription is coordinately increased at spatially distinct promoters, however, remains poorly understood. Using the murine immunoglobulin lambda (Igλ) locus as model, we find that three enhancer-like elements in the 3' Igλ domain, Eλ3-1, HSCλ1 and HSE-1, show strikingly similar transcription factor binding dynamics and close spatial proximity, suggesting that they form an active enhancer hub. Temporal analyses show coordinate recruitment of complementary V and J gene segments to this hub, with comparable transcription factor binding dynamics to that at enhancers. We find further that E2A, p300, Mediator and Integrator bind to enhancers as early events, whereas YY1 recruitment and eRNA synthesis occur later, corresponding to transcription activation. Remarkably, the interplay between sense and antisense enhancer RNA is central to both active enhancer hub formation and coordinate Igλ transcription: Antisense Eλ3-1 eRNA represses Igλ activation whereas temporal analyses demonstrate that accumulating levels of sense eRNA boost YY1 recruitment to stabilise enhancer hub/promoter interactions and lead to coordinate transcription activation. These studies therefore demonstrate for the first time a critical role for threshold levels of sense versus antisense eRNA in locus activation.

| S-EPMC10602925 | biostudies-literature

Multiple myeloma immunoglobulin lambda translocations portend poor prognosis

Project description:Multiple myeloma immunoglobulin lambda translocations portend poor prognosis

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Multiple myeloma immunoglobulin lambda translocations portend poor prognosis

Project description:Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years. To better understand and identify these ‘high-risk’ cases, we analyzed the translocation landscape of myeloma from 795 newly-diagnosed patients by whole genome sequencing from the CoMMpass study. Translocations involving the immunoglobulin lambda (IgL) locus were identified in 10% of patients, and were indicative of poor prognosis. Importantly, 70% of IgL translocations co-occurred with hyperdiploid disease, a marker of standard risk, potentially resulting in the misclassification of IgL-translocated myeloma. Most IgL-translocations coincided with focal amplifications that were centered on the 3’ enhancer. Patients with IgL-translocations failed to benefit from immunomodulatory imide drugs (IMiDs), which target the lymphocyte-specific transcription factor IKZF1 that is bound to the IgL 3’ enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL-translocation as a driver of poor prognosis which may be due in part to IMID resistance.

2019-03-13 | GSE121912 | GEO

Lambdavirus lambda

Project description:Lambdavirus lambda

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Lambdavirus lambda

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Lambdavirus lambda

Project description:Lambdavirus lambda Genome sequencing

| PRJNA274640 | ENA

Lambdavirus lambda

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Total gene expression analysis of LMP2A/λ-MYC and λ-MYC tumors

2011-10-26 | GSE26918 | GEO

Total gene expression analysis of LMP2A/λ-MYC and λ-MYC tumors

Project description:We have developed a transgenic mouse model for Epstein-Barr virus-associated Burkitt's lymphoma. Transgenic mice that express LMP2A and MYC in B cells develop spontaneous lymph node tumors at different rates. Tumor onset occurs at approximately 40-60 days in LMP2A/λ-MYC mice and at 100-200 days in λ-MYC mice. This study compared total gene expression in the tumor cells from each genotype, as well as in B cells isolated from 3 week old mice prior to tumor onset. Comparison of total gene expression in tumor cells from LMP2A/λ-MYC and λ-MYC transgenic mice identified a short list of differentially expressed genes. Comparison of gene expression in B cells from the spleens of 3 week old mice, in contrast, identified a 10-fold increase in the number of differentially expressed genes. B cells from the spleens of 3 week old LMP2A/λ-MYC (n=5), λ-MYC (n=5), LMP2A (n=3), and WT (n=3) transgenic mice were purified using magnetic-activated cell sorting (MACS) beads purchased from Miltenyi for CD19 positive selection. Total RNA was isolated from these purified B cells, as well as from cervical lymph node tumor cells that developed in LMP2A/λ-MYC (n=7) and λ-MYC (n=5) transgenic mice using RNeasy RNA extraction kit from QIAGEN. Cervical lymph node tumor cells were >90% positive for the B cell marker B220, and were not further purified. Total gene expression was assessed in each sample, along with heart and brain reference samples using MouseRef-8 v2.0 Expression Bead Chips purchased from Illumina. GeneSpring analysis software was used to analyze the expression data and identify significantly differentially expressed genes (fold change >1.5-fold and false discovery rate< 0.05).

2011-10-25 | E-GEOD-26918 | biostudies-arrayexpress

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