Similar Datasets
Project description:Dynamic changes to the epigenome are essential regulators of B cell differentiation and, when perturbed, can lead to cancer. We compared three types of mature B cell lymphoma/leukemia (BCL) and normal lymphocytes to identify common and distinct epigenetic perturbations that promote oncogenesis. Purified malignant B cells from 52 patients (18 Follicular, 11 Diffuse Large B Cell, 23 Chronic Lymphocytic Lymphomas) and normal B cell subsets from 28 donor tonsils were subjected to chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K9/14ac, and H3K27ac; FAIRE-seq for open chromatin; RNA-seq; and genome copy number arrays. We identified a novel super enhancer (SE) connected to the aberrant expression of FCMR and PIGR in multiple BCL subtypes, which may drive the tissue-specific expression of the two immunoglobulin receptor genes. These integrative studies also revealed that loss of normal B cell SEs in BCL was associated with significant reduction in linked gene expression, the greatest impact among regulatory elements. Downregulation of crucial B cell transcription factors (TF) and tumor suppressors was consistent across BCL subtypes and linked to significantly diminished or absent active chromatin marks in adjacent SEs. These BCL-repressed SEs are enriched in binding sites for the same suppressed TFs that they regulate, suggesting transcriptional regulatory feedback loops for these key B cell identity genes. In sum, this study defined common alterations in the regulomes of mature B cell leukemias and lymphomas and implicate SEs as important hubs of tumor suppressing transcriptional feedback loops that are perturbed in B cell cancer.
2021-09-02 | GSE145847 | GEO
Project description:Dynamic changes to the epigenome are essential regulators of B cell differentiation and, when perturbed, can lead to cancer. We compared three types of mature B cell lymphoma/leukemia (BCL) and normal lymphocytes to identify common and distinct epigenetic perturbations that promote oncogenesis. Purified malignant B cells from 52 patients (18 Follicular, 11 Diffuse Large B Cell, 23 Chronic Lymphocytic Lymphomas) and normal B cell subsets from 28 donor tonsils were subjected to chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K9/14ac, and H3K27ac; FAIRE-seq for open chromatin; RNA-seq; and genome copy number arrays. We identified a novel super enhancer (SE) connected to the aberrant expression of FCMR and PIGR in multiple BCL subtypes, which may drive the tissue-specific expression of the two immunoglobulin receptor genes. These integrative studies also revealed that loss of normal B cell SEs in BCL was associated with significant reduction in linked gene expression, the greatest impact among regulatory elements. Downregulation of crucial B cell transcription factors (TF) and tumor suppressors was consistent across BCL subtypes and linked to significantly diminished or absent active chromatin marks in adjacent SEs. These BCL-repressed SEs are enriched in binding sites for the same suppressed TFs that they regulate, suggesting transcriptional regulatory feedback loops for these key B cell identity genes. In sum, this study defined common alterations in the regulomes of mature B cell leukemias and lymphomas and implicate SEs as important hubs of tumor suppressing transcriptional feedback loops that are perturbed in B cell cancer.
2021-09-02 | GSE145846 | GEO
Project description:Dynamic changes to the epigenome are essential regulators of B cell differentiation and, when perturbed, can lead to cancer. We compared three types of mature B cell lymphoma/leukemia (BCL) and normal lymphocytes to identify common and distinct epigenetic perturbations that promote oncogenesis. Purified malignant B cells from 52 patients (18 Follicular, 11 Diffuse Large B Cell, 23 Chronic Lymphocytic Lymphomas) and normal B cell subsets from 28 donor tonsils were subjected to chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K9/14ac, and H3K27ac; FAIRE-seq for open chromatin; RNA-seq; and genome copy number arrays. We identified a novel super enhancer (SE) connected to the aberrant expression of FCMR and PIGR in multiple BCL subtypes, which may drive the tissue-specific expression of the two immunoglobulin receptor genes. These integrative studies also revealed that loss of normal B cell SEs in BCL was associated with significant reduction in linked gene expression, the greatest impact among regulatory elements. Downregulation of crucial B cell transcription factors (TF) and tumor suppressors was consistent across BCL subtypes and linked to significantly diminished or absent active chromatin marks in adjacent SEs. These BCL-repressed SEs are enriched in binding sites for the same suppressed TFs that they regulate, suggesting transcriptional regulatory feedback loops for these key B cell identity genes. In sum, this study defined common alterations in the regulomes of mature B cell leukemias and lymphomas and implicate SEs as important hubs of tumor suppressing transcriptional feedback loops that are perturbed in B cell cancer.
2021-09-02 | GSE145842 | GEO
Project description:Dynamic changes to the epigenome are essential regulators of B cell differentiation and, when perturbed, can lead to cancer. We compared three types of mature B cell lymphoma/leukemia (BCL) and normal lymphocytes to identify common and distinct epigenetic perturbations that promote oncogenesis. Purified malignant B cells from 52 patients (18 Follicular, 11 Diffuse Large B Cell, 23 Chronic Lymphocytic Lymphomas) and normal B cell subsets from 28 donor tonsils were subjected to chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K9/14ac, and H3K27ac; FAIRE-seq for open chromatin; RNA-seq; and genome copy number arrays. We identified a novel super enhancer (SE) connected to the aberrant expression of FCMR and PIGR in multiple BCL subtypes, which may drive the tissue-specific expression of the two immunoglobulin receptor genes. These integrative studies also revealed that loss of normal B cell SEs in BCL was associated with significant reduction in linked gene expression, the greatest impact among regulatory elements. Downregulation of crucial B cell transcription factors (TF) and tumor suppressors was consistent across BCL subtypes and linked to significantly diminished or absent active chromatin marks in adjacent SEs. These BCL-repressed SEs are enriched in binding sites for the same suppressed TFs that they regulate, suggesting transcriptional regulatory feedback loops for these key B cell identity genes. In sum, this study defined common alterations in the regulomes of mature B cell leukemias and lymphomas and implicate SEs as important hubs of tumor suppressing transcriptional feedback loops that are perturbed in B cell cancer.
2021-09-02 | GSE145841 | GEO
Project description:Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers
| PRJNA608506 | ENA
Project description:Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers (RNA array)
| PRJNA608514 | ENA
Project description:Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers (SNP array)
| PRJNA608515 | ENA
Project description:Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers (RNA-seq)
| PRJNA608516 | ENA
Project description:Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers (ChIP-seq, FAIRE-seq)
| PRJNA608513 | ENA
Project description:Estrogen receptor α (ERα) modulates gene expression by interacting with chromatin regions that are frequently distal from the promoters of estrogen-regulated genes. Active chromatin-enriched "super-enhancer" (SE) regions, mainly observed in in vitro culture systems, often control production of key cell type-determining transcription factors. Here, we defined super-enhancers that bind to ERα in vivo within hormone-responsive uterine tissue in mice. We found that SEs are already formed prior to estrogen exposure at the onset of puberty. The genes at SEs encoded critical developmental factors, including retinoic acid receptor α (RARA) and homeobox D (HOXD). Using high-throughput chromosome conformation capture (Hi-C) along with DNA sequence analysis, we demonstrate that most SEs are located at a chromatin loop end and that most uterine genes in loop ends associated with these SEs are regulated by estrogen. Although the SEs were formed before puberty, SE-associated genes acquired optimal ERα-dependent expression after reproductive maturity, indicating that pubertal processes that occur after SE assembly and ERα binding are needed for gene responses. Genes associated with these SEs affected key estrogen-mediated uterine functions, including transforming growth factor β (TGFβ) and LIF interleukin-6 family cytokine (LIF) signaling pathways. To the best of our knowledge, this is the first identification of SE interactions that underlie hormonal regulation of genes in uterine tissue and optimal development of estrogen responses in this tissue.
| S-EPMC7307205 | biostudies-literature