EXPERIMENT_TITLE: GSM4453812: SCABER_HiC; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C was performed using the Arima-HiC kit as per the manufacturer's protocol. Briefly, 1 million fresh and detached cells or 20mg tumor tissue (frozen and pulverized) was cross-linked with 1% formaldehyde, restriction enzyme digested, Biotin-14-dATP end-labeled , and subsequently ligated.  Ligated chromatin product was then reverse-crosslinked, sonicated (Covaris E220) to 300–500 bp fragments, pulled down with dynabeads Streptavidin  C1 beads. Hi-C DNA was then processed using Kapa Hyper Prep Kit where it was end repaired, adenylated, adaptor ligated, and PCR amplified with KAPA DNA library prepare kit. Pair-end 2x50/2x100/2x150 bp high-throughput sequencing was performed using HiSeq/NovaSeq platform (Illumina).
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. Transcriptionally, FOXA1, GATA3, and PPARg are shown to be essential for luminal subtype-specific gene regulation and subtype switching, while TP63, STAT3 and TFAP2 family members are critical for regulation of basal subtype-specific genes. Despite these advances, the underlying epigenetic mechanisms and 3D chromatin architecture responsible for subtype-specific regulation in bladder cancer remains unknown. Result: We determine the genome-wide transcriptome, enhancer landscape and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer.   Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration. Conclusion: In summary, our work identifies unique epigenomic signatures and 3D genome structures in luminal and basal urinary bladder cancers and suggests a novel link between the circadian transcription factor NPAS2 and a clinical bladder cancer subtype. Overall design: We performed epigenomic analysis including RNA-Seq, H3K27ac ChIP-Seq, GATA3 ChIP-Seq, ATAC-Seq and Hi-C on molecular subtypes of bladder cancer cell lines and 5 patient tumors. Raw data for tumor samples not provided due to patient privacy concerns.
SAMPLE_TITLE: SCABER_HiC
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Cell"}, {"TAG": "sample type", "VALUE": "Cell Line; SCABER; Bladder Cancer"}, {"TAG": "chip-seq antibody", "VALUE": "none"}]
Pool_Member_@attributes_sample_title: SCABER_HiC
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