{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["N/A"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00001004046"],"sample_count":["303"],"description":["EGA dataset EGAD00001004046"],"repository":["EGA"],"title":["Reference Epigenomes and Regulatory Landscape of CLL"],"pubmed_abstract":["While analyzing the DNA methylome of multiple myeloma (MM), a plasma cell neoplasm, by whole-genome bisulfite sequencing and high-density arrays, we observed a highly heterogeneous pattern globally characterized by regional DNA hypermethylation embedded in extensive hypomethylation. In contrast to the widely reported DNA hypermethylation of promoter-associated CpG islands (CGIs) in cancer, hypermethylated sites in MM, as opposed to normal plasma cells, were located outside CpG islands and were unexpectedly associated with intronic enhancer regions defined in normal B cells and plasma cells. Both RNA-seq and in vitro reporter assays indicated that enhancer hypermethylation is globally associated with down-regulation of its host genes. ChIP-seq and DNase-seq further revealed that DNA hypermethylation in these regions is related to enhancer decommissioning. Hypermethylated enhancer regions overlapped with binding sites of B cell-specific transcription factors (TFs) and the degree of enhancer methylation inversely correlated with expression levels of these TFs in MM. Furthermore, hypermethylated regions in MM were methylated in stem cells and gradually became demethylated during normal B-cell differentiation, suggesting that MM cells either reacquire epigenetic features of undifferentiated cells or maintain an epigenetic signature of a putative myeloma stem cell progenitor. Overall, we have identified DNA hypermethylation of developmentally regulated enhancers as a new type of epigenetic modification associated with the pathogenesis of MM."],"pubmed_title":["Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers."],"pubmed_authors":["Agirre Xabier X, Castellano Giancarlo G, Pascual Marien M, Heath Simon S, Kulis Marta M, Segura Victor V, Bergmann Anke A, Esteve Anna A, Merkel Angelika A, Raineri Emanuele E, Agueda Lidia L, Blanc Julie J, Richardson David D, Clarke Laura L, Datta Avik A, Russiñol Nuria N, Queirós Ana C AC, Beekman Renée R, Rodríguez-Madoz Juan R JR, San José-Enériz Edurne E, Fang Fang F, Gutiérrez Norma C NC, García-Verdugo José M JM, Robson Michael I MI, Schirmer Eric C EC, Guruceaga Elisabeth E, Martens Joost H A JH, Gut Marta M, Calasanz Maria J MJ, Flicek Paul P, Siebert Reiner R, Campo Elías E, Miguel Jesús F San JF, Melnick Ari A, Stunnenberg Hendrik G HG, Gut Ivo G IG, Prosper Felipe F, Martín-Subero José I JI"],"name_synonyms":["Vasp, VASP, DmelCG15112, ENHANCER OF ATNSI ACTIVITY, Data Set, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, 2018., ENA/VASP"],"description_synonyms":["CLL Lymphoplasmacytoid Lymphomas, H2S(D2S), B Cells, Chronic B-Cell, determination, Palatine Tonsils, Plasmacytes, Bursa-Dependent Lymphocytes, Chronic B-Lymphocytic, Visible Light, Lymphatic Leukemia, DNA Methylations, Tumor, B Cell, Small, Histone H2b, Histone H2a, Whole Transcriptome, Transcriptome Sequencing, Lymphoplasmacytoid Lymphoma, Chronic Lymphocytic Leukemias, Lymphomas, Chromatins, chronic lymphatic, ChIA-PET, average, Palatine, Centers, Chromatin Immunoprecipitation Sequencing Chip, thymus nucleic acid, Chromatin Immuno precipitation Sequencing, DNA methylation maintenance, Gene Expressions, B-cell chronic lymphocytic leukemia, Genomes, Small-Cell Lymphomas, Germinal, ChIP, ATAC-seq, Complete Exome Sequencing, Chromatin Immuno Precipitation Paired End Tag, Whole Transcriptome Sequencing, CLL Lymphoplasmacytoid Lymphoma, Plasmacytoid, Small Lymphocytic Lymphoma, Well-Differentiated Lymphocytic Lymphoma, B-Lymphocytic Leukemia, DNA methylation, adult chronic leukaemia, Lymphoblastic Leukemias, Chromatin Immunoprecipitation Paired-End Tag, Center, TNFSF14, Chronic Lymphatic Leukemias, B lymphocyte, malignant neoplasm, chromosome scaffold, ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, adult chronic leukemia, Histone H5, Histone H4, Histone H7, Malignancies, Double-Stranded DNA, deoxyribonucleic acids, chronic lymphatic leukaemia, DNAn, Plasma Cell, Histone H1, Mandel, Histone H3, Tumors, nuclear chromatin, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, B-Cell Chronic Lymphocytic Leukemia, Radiation, wide/broad, B Lymphocytes, UNQ391/PRO726, mature B-cell, B Cell Malignancy, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, Exome, B-cell differentiation, Maps, RNA-seq, Light, Low-Grade B-Cell Malignancies, Double-Stranded, ChIP-PET, lymphoplasmacytic leukemia, (Deoxyribonucleotide)n+m, lymhpoid nodule, LIGHT, Benign, B-Cell Malignancies, B Lymphocytic Leukemia, lymph node central zone, chronic lymphatic leukemia, B Cell Chronic Lymphocytic Leukemia, B Cell Leukemia, lymphocytic, lymph node nodule, desoxyribose nucleic acid, Visible Radiations, Lymphoblastic Leukemia, Complete Transcriptome, Visible Radiation, Lymphatic Leukemias, HVEML, ATAC-seq assay, Well-Differentiated Lymphocytic Lymphomas, Disrupted In B-Cell Malignancy, Chronic Lymphoblastic, Benign Neoplasms, whole genome, ChIP Exonuclease, Chronic Lymphoblastic Leukemias, mature B-lymphocyte, Low-Grade B-Cell Malignancy, Plasmacyte, Malignant Neoplasms, wide, B-Lymphocyte, Lymphoplasmacytoid, B cell development, CLL Lymphoplasmacytoid, Lymphoma, Cells, ds DNA, Whole Exome Sequencing, chronic lymphocytic leukaemia, DNA, ChIP-Exonuclease, Transcriptome Sequencings, Methylation, Small Lymphocytic Lymphomas, Lymphoplasmacytoid Lymphomas, CLL, Cll, cytoplasmic chromatin, Chronic B-Cell Leukemia, ChIP-Chip, DNS, Chromatin Immuno-precipitation, Lymphocytic Leukemia, (Deoxyribonucleotide)n, nodule, Complete Exome, Neoplasms, B-Lymphocytic Leukemias, Benign Neoplasm, chronic LYMPHOCYTIC, B-Cell, Gene, CLIP-Seq, broad, Assay for Transposase-Accessible Chromatin Using Sequencing, Malignant, B-cell chronic lymphocytic leukaemia, Deoxyribonucleic acids, Ly113, cll, CML, Tonsils, Deoxyribonucleic Acid, B-cell chronic lymphoid leukemia, Chromatin Immunoprecipitation Sequencing-Chip, Whole Transcriptome Shotgun Sequencing, Chronic B-Cell Leukemias, Well-Differentiated Lymphocytic, Well Differentiated, Histone H3.3, Low-Grade, Genomes., Lymphocytic, WES, B-cell, Leukemia, Complete, B-lymphocyte differentiation, Exome Sequencings, Malignancy, Chromatin Immunoprecipitation Paired End Tag, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, Double Stranded, bisulfite, Deoxyribonucleic acid, Visible, Small-Cell Lymphoma, Expressions, Sequencing, Ect5, Diffuse, Neoplasias, Tonsil, Whole Exome, Disrupted In B Cell Malignancy, B lymphocyte differentiation, Whole, Chronic, Diffuse Well Differentiated Lymphocytic Lymphoma, TR2, Chronic B-Lymphocytic Leukemias, (Deoxyribonucleotide)m, Expression, Chronic Lymphocytic, Diffuse Well-Differentiated Lymphocytic Lymphoma, Low Grade, Methylations, CG7937, Cancer, leukemia, HITS-CLIP, WGS, Complete Exome Sequencings, Malignant Neoplasm, whole blood, hydrosulfite, DNAn+1, Small Cell, tonsilla palatina, Chronic Lymphocytic Leukemia, lymphoplasmacytic leukaemia, Chronic B-Lymphocytic Leukemia, B-Cell Malignancy, 311, ChIP Sequencing, Chronic Lymphoblastic Leukemia, CD258, Histone, chronic, Leukemias, Cell, B-Cell Leukemia, ChIP-Exo, Exome Sequencing, Well-Differentiated, H3K4me3, Chronic Lymphatic, MT, 93Bal, Small Cell Lymphoma, Germinal Centers, chemical analysis, Lymphocytic Leukemias, Neoplasm, mature B lymphocyte, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, ds-DNA, Low-Grade B-Cell, Radiations, Chronic Lymphatic Leukemia, Plasma, small lymphocytic lymphoma, primary cancer, c15, Complete Transcriptome Sequencing, Lymphocytic Lymphomas, HVEM-L, DmelCG7937, B-Cell Leukemias, Photoradiation, Lymphoblastic, Chromatin Immunoprecipitation, Bursa-Equivalent Lymphocyte, Small Lymphocytic, Chromatin Immuno-precipitation Sequencing, Cancers, ChIP-Seq, Histone H1(s), malignant tumor, LTg, Assay for Transposase Accessible Chromatin Using Sequencing, Small-Cell, Hox11-311, Photoradiations, Lymphocytic Lymphoma, Chromatin Immuno-Precipitation Paired-End Tag, Desoxyribonukleinsaeure, assay, B-lymphocyte, Neoplasia, lymph node activated zone"],"pubmed_title_synonyms":["Plasma-Cell Myelomas, Plasma-cell myeloma, Disease, B Cells, Myelomas, determination, B Lymphocytes, Methylomes, Myeloma, Multiple myeloma (disorder), Kahler's disease, Cell Myelomas, B cell, Myeloma Multiple, Myeloma-Multiples, Myeloma-Multiple, Bursa-Dependent Lymphocytes., Multiple Myeloma, MM, Al amyloidosis, multiple myeloma, Kahler, Multiple Myelomas, chemical analysis, [M]Plasma cell myeloma, Myelomatoses, NOS, Myelomatosis, Methylome, MULT MYELM W/O REMISSION, morphology (morphologic abnormality), Plasma-Cell, Plasma-Cell Myeloma, Plasmacytic myeloma, systemic, Plasma, amyloidosis, B-cell, Multiple myeloma, Epigenomes, Plasma Cell Myelomas, myeloma, Kahler Disease, Bursa-Equivalent Lymphocyte, DNA Methylomes, Multiple myeloma without mention of remission, Multiple, no ICD-O subtype, Cell Myeloma, multiple, B lymphocyte, Plasma Cell Myeloma, no ICD-O subtype (morphologic abnormality), B-Lymphocyte, assay, DNA, Multiple myeloma (clinical), B-lymphocyte, Plasma Cell, myeloma - multiple, DNA Methylome"],"pubmed_abstract_synonyms":["H2S(D2S), MGC130048, host organism, B Cells, Materials, degree (angle), Plasmacytes, Bursa-Dependent Lymphocytes, Cell Myelomas, B cell, positive regulation by symbiont of host non-apoptotic programmed cell death, A4, Tumor, Myeloma-Multiples, Myeloma-Multiple, Downregulation, plasmacytic neoplasm, Mother Cells, pathogenesis, plasmacytic tumour, DNaseI-Seq, ChIA-PET, systemic, average, gamma sarcoglycan, amyloidosis, Chromatin Immunoprecipitation Sequencing Chip, plasma cell tumor, Chromatin Immuno precipitation Sequencing, stimulation by symbiont of host programmed cell death, Genomes, ChIP, Chromatin Immuno Precipitation Paired End Tag, myeloma, DNA Methylomes, high grade, Epigenomic, Chromatin Immunoprecipitation Paired-End Tag, CpG Clusters, Cell Myeloma, B lymphocyte, no ICD-O subtype (morphologic abnormality), malignant neoplasm, \"Plasmacytic tumor\" EXACT [NCI2004_11_17:C4665], ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, gamma-sarcoglycan, Malignancies, associated, Plasma Cell, Tumors, Plasma-Cell Myelomas, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, CpG-Rich Islands, Myelomas, B Lymphocytes, Methylomes, Myeloma, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, B-cell differentiation, SG-gamma, RNA-seq, Clusters, ChIP-PET, Multiple Myeloma, Binding, Kahler, Benign, Colony-Forming Unit, Receptor Down-Regulation, Stem Cell, modulation by symbiont of host system process, Genetic Materials, NOS, sarcoglycan, Methylome, morphology (morphologic abnormality), Genetic Material, Plasma-Cell Myeloma, Mother Cell, \"Plasma cell disorder (disorder)\" EXACT [SNOMEDCT_2005_07_31:277576009], Factors, Epigenetic, Stem, Heterogeneity, Benign Neoplasms, Colony Forming Units, whole genome, ChIP Exonuclease, gamma (35kDa dystrophin-associated glycoprotein), Islands, plasmacytic tumor, CpG-Rich Island, Malignant Neoplasms, Plasmacyte, animal stem cell, Multiple, \"Plasma cell dyscrasia (disorder)\" EXACT [SNOMEDCT_2005_07_31:71390001], DMDA, multiple, Cluster, B-Lymphocyte, Material, 35kD dystrophin-associated glycoprotein, B cell development, activation by symbiont of host programmed cell death, Cells, Cistron, DNA, Multiple myeloma (clinical), Epigenetics, ChIP-Exonuclease, DNA Methylome, ChIP-Chip, SGCG_HUMAN, Chromatin Immuno-precipitation, DNase I hypersensitive sites sequencing, Multiple myeloma (disorder), Kahler's disease, Neoplasms, regulation by symbiont of host system process, Colony-Forming Units, Benign Neoplasm, Progenitor Cell, Gene, CLIP-Seq, Assay for Transposase-Accessible Chromatin Using Sequencing, Malignant, Transcription Factor, TYPE, plasma cell tumour, DAGA4, Multiple Myelomas, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, Genetic heterogeneity, Island, [M]Plasma cell myeloma, \"Plasma cell neoplasm (morphology)\" EXACT [SNOMEDCT_2005_07_31:127580003], Chromatin Immunoprecipitation Sequencing-Chip, Sites, 35DAG, Myelomatoses, Whole Transcriptome Shotgun Sequencing, causality., MAM, gamma-SG, SCG3, Progenitor, Plasmacytic myeloma, Site, CpG Cluster, Transcription, \"Plasma cell tumour\" EXACT [SNOMEDCT_2005_07_31:274907000], B-cell, Multiple myeloma, B-lymphocyte differentiation, pattern, Genetic, Malignancy, plasma cell dyscrasia, distribution, Chromatin Immunoprecipitation Paired End Tag, Plasma Cell Myelomas, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, bisulfite, Mother, causes, CpG, Sequencing, Neoplasias, Combining Site, plasma cell neoplasm, B lymphocyte differentiation, Combining Sites, Methylations, myeloma - multiple, Cancer, Plasma-cell myeloma, HITS-CLIP, Disease, Colony Forming Unit, activation by organism of non-apoptotic programmed cell death in other organism, Malignant Neoplasm, 35 kDa dystrophin-associated glycoprotein, hemolysin activity, hydrosulfite, malignant, Progenitor Cells, \"Plasma cell neoplasm (disorder)\" EXACT [SNOMEDCT_2005_07_31:415111003], ChIP Sequencing, Myeloma Multiple, Factor, Binding Site, Cistrons, Cell, Down Regulation, ChIP-Exo, SGCG, LGMD2C, MM, Al amyloidosis, multiple myeloma, Down-Regulation, MT, Down-Regulation (Physiology), Neoplasm, Myelomatosis, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, methylation, MULT MYELM W/O REMISSION, Plasma-Cell, Plasma, primary cancer, CpG Island, DMDA1, Epigenomes, Kahler Disease, Chromatin Immunoprecipitation, Combining, stem cell, plasma cell disorder, Bursa-Equivalent Lymphocyte, Chromatin Immuno-precipitation Sequencing, Cancers, arc degree, ChIP-Seq, malignant tumor, Assay for Transposase Accessible Chromatin Using Sequencing, Multiple myeloma without mention of remission, CpG Rich Islands, no ICD-O subtype, Plasma Cell Myeloma, Chromatin Immuno-Precipitation Paired-End Tag, SCARMD2, Receptor, B-lymphocyte, Neoplasia, DNase-Seq, CpG-Rich"],"additional_accession":[]},"is_claimable":false,"name":"ena-DATASET-BLUEPRINT-16-03-2018-14:03:53:512-282 - samples","description":"Analysis of the reference epigenomes and regulatory landscape of CLL as a whole and its major clinico-biological subtypes (with mutated and unmutated IGHV) in the light of the normal B-cell differentiation.\n\nWe have extensively characterized the reference epigenomes of seven primary chronic lymphocytic leukemia samples (CLLs) with mutated (n=5) and unmutated IGHV (n=2) as well as several mature B-cell subpopulations (naive B cells from blood and tonsil, germinal center B cells, memory B cells and plasma cells from tonsil) using genome-wide maps of six histone marks (H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K9me3 and H3K27me3), DNA accessibility (ATAC-seq), DNA methylation (whole-genome bisulfite sequencing) and gene expression (RNA-seq). Furthermore, we have mapped the regulatory chromatin landscape of 100 additional CLL cases using chIP-seq of H3K27ac and ATAC-seq and linked these data to additional layers of information (whole-genome and/or whole-exome sequencing (WGS/WES), RNA-seq and DNA methylation microarrays) studied in the context of the International Cancer Genome Consortium (ICGC).","dates":{"updated":"2020-05-12 09:48:35"},"accession":"EGAD00001004046","cross_references":{"TAXONOMY":["9606"],"pubmed":["25644835"],"EGA":["EGAC00001000135","EGAS00001000326","EGAS00001000327","EGAS00001000418","EGAS00001001110","EGAS00001001596"]}}