EXPERIMENT_TITLE: GSM5981806: HiC_UT242; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C libraries were prepared based on the in situ Hi-C protocol 16 with minor modifications. Briefly, 5 x 106 cells were cross-linked with 1% formaldehyde (Sigma #252549) for 10 min with gentle rotation and quenched with 125 mM glycine. Cells were washed twice with ice-cold PBS and cells were snap-frozen on dry ice for 30 min. Cell pellets were resuspended in 1 mL ice-cold cell lysis buffer and rotated for 30 min at 4°C.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Structural variants (SVs) involving enhancer hijacking can disrupt chromatin topologies to cause oncogene activation in cancer genomes, yet the molecular determinants for the transcriptional output of enhancer hijacking remain largely unknown. We developed a multimodal approach to integrate genome sequencing, chromosome conformation, and sequence-based deep learning for quantitative analysis of transcriptional effects and structural reorganization imposed by SVs in leukemic genomes. We identified candidate pathogenic SVs including recurrent t(5;14) translocations that cause the hijacking of BCL11B enhancers for oncogenic activation of TLX3-dependent transcriptional programs. By engineering patient-associated t(5;14) in isogenic leukemia cells, we uncovered an uncharacterized mechanism whereby DNA methylation serves as an epigenetic barrier to enhancer hijacking and loss of epigenetic barrier is a molecular determinant for the transcriptional output of pathogenic SVs. Hence, leveraging the epigenetic barriers of SV-mediated oncogenic programs may provide new opportunities to reprogram gene regulation as epigenetic therapies in human disease. Overall design: We performed Hi-C experiments for leukemia cells from UT424 with TLX3 translocation
SAMPLE_TITLE: HiC_UT242
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Leukemia cells"}, {"TAG": "tissue", "VALUE": "Leukemia cells"}]
Pool_Member_@attributes_sample_title: HiC_UT242
RUN_SET_RUN_Pool_Member_@attributes_sample_title: HiC_UT242
RUN_SET_RUN_SRAFiles_SRAFile: [{"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR18518542.lite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos2/sra-pub-zq-18/SRR018/18518/SRR18518542/SRR18518542.lite.1", "size": "12811107425", "date": "2022-10-23 15:07:23", "md5": "b1ee27e2d8df81ac80fb2af2c3da8329", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR18518542", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR18518542/SRR18518542", "size": "18470868261", "date": "2022-05-11 17:05:09", "md5": "3179bf3187fb11304f1656c0e70b506f", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}]