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Series GSE69558 Query DataSets for GSE69558
Status Public on Aug 04, 2015
Title Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary B-cell lymphomas frequently demonstrate inter-chromosomal translocations that lead to oncogene activation by heterologous distal regulatory elements. We utilized a novel approach, termed ‘Pinpointing of Enhancer-Associated Rearrangements by Chromatin Immunoprecipitation’ or PEAR-ChIP, to simultaneously map enhancer activity and proximal rearrangements in lymphoma cell lines and patient biopsies. The method efficiently detects rearrangements within and adjacent to known cancer genes such as CCND1, BCL2, MYC, PDCD1LG2, NOTCH1, CIITA, and SGK1, as well as novel enhancer duplication events of likely oncogenic significance. We identify novel enhancer-like elements in the MYC locus that interact with the MYC promoter, are associated with germline polymorphisms that alter lymphoma risk, show lymphoma subtype-specific acetylation, and are silenced in lymphomas where MYC is activated by “enhancer hijacking” translocations. We also identify an array of BCL6-interacting enhancers that are subject to genomic alterations, are acetylated by the BCL6-activating transcription factor MEF2B, and target the MYC promoter in the context of a “pseudo-double-hit” t(3;8) genomic rearrangement linking the BCL6 and MYC loci. Our findings uncover diverse mechanisms by which genomic rearrangements can lead to aberrations in enhancer-mediated oncogene regulation.
Overall design Examination of histone modifications and transcription factors in lymphoma cell lines and primary patient samples
Contributor(s) Ryan RJ, Drier Y, Bernstein BE
Citation(s) 26229090
Submission date Jun 04, 2015
Last update date Nov 01, 2021
Contact name Yotam Drier
Organization name The Hebrew University of Jerusalem
Department Immunology and Cancer Research
Lab Drier
Street address Faculty of Medicine, The Hebrew University, Ein Kerem
City Jerusalem
State/province Israel
ZIP/Postal code 9112102
Country Israel
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (70)
GSM1703890 DB Input
GSM1703891 DB MEF2B ab33540
GSM1703892 DB MEF2B HPA004734
BioProject PRJNA285847
SRA SRP059064

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Supplementary file Size Download File type/resource
GSE69558_RAW.tar 17.3 Gb (http)(custom) TAR (of TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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