EXPERIMENT_TITLE: GSM6995359: MDA-MB-231, 75 nM THZ1, 48 hr, rep 1; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Per each sample, 7-10 x 106 cells were crosslinked with 4% formaldehyde. Crosslinked chromatin was digested using a proprietary restriction enzyme cocktail and then labeled with biotinylated nucleotide by Arima Genomics. DNA fragments were subjected to a custom library protocol utilizing Swift Biosciences Accel-NGS 2S Plus DNA Library Kit (Cat # 26148, 26248, 26396, 26596, 26696, 26796, 26896, or 269384) to produce Arima-HiC libraries for sequencing.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Cyclin Dependent Kinase 7 (CDK7) is the core catalytic subunit of Cyclin Activating Kinase (CAK), a complex that has dual roles in cell cycle progression and transcription. While several CDK7 inhibitors are efficacious in preclinical models of cancer and have entered clinical trials, the mechanism(s) by which CDK7 promotes proliferation and cell viability is not well understood. Using triple negative breast cancer (TNBC) as a model, we found that inhibiting CDK7, either genomically or pharmacologically, induces mitotic dysfunction. Live and static cell imaging revealed that CDK7 inhibition prolongs mitosis and induces chromatin bridge formation, DNA double strand breaks, and abnormal nuclear features, all of which are indicative of mitotic catastrophe and chromosome instability. Transcriptome analyses revealed that CDK7 is essential for maintaining condensin complex gene expression, suggesting that CDK7 may sustain chromatin configuration, a role that extends beyond its impact on super-enhancers. Indeed, inhibiting CDK7 alters chromatin architecture consistent with condensin disruption. Confirming the importance of condensin regulation by CDK7, genetic suppression of a core subunit of this complex, structural maintenance of chromosome 2 (SMC2), phenocopies CDK7 inhibition. We report an undescribed role of CDK7 in maintaining chromatin structure and chromosome stability, as well as promoting proper mitoses, by sustaining condensin expression. Overall design: Hi-C study MDA-MB-231 cells treated with DMSO (Vehicle, Control) or THZ1 (CDK7 inhibitor, drug) in technical replicates.
SAMPLE_TITLE: MDA-MB-231, 75 nM THZ1, 48 hr, rep 1
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "MDA-MB-231"}, {"TAG": "cell line", "VALUE": "MDA-MB-231"}, {"TAG": "cell type", "VALUE": "triple negative breast cancer cells"}, {"TAG": "genotype", "VALUE": "WT"}, {"TAG": "treatment", "VALUE": "THZ1, 75 nM"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: MDA-MB-231, 75 nM THZ1, 48 hr, rep 1
RUN_SET_RUN_Pool_Member_@attributes_sample_title: MDA-MB-231, 75 nM THZ1, 48 hr, rep 1
RUN_SET_RUN_SRAFiles_SRAFile: [{"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR23242631.lite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos5/sra-pub-zq-16/SRR023/23242/SRR23242631/SRR23242631.lite.1", "size": "44055488635", "date": "2023-02-03 05:24:05", "md5": "f9d55a43ff0aa3ed484aa8bccefe16bb", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR23242631", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR23242631/SRR23242631", "size": "62602008899", "date": "2023-01-27 00:57:53", "md5": "c9925a8540049c85a27154c9fe08e672", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "THZ1_1_R2.fastq.gz", "size": "48778405495", "date": "2023-01-27 00:43:58", "md5": "222305d0ba25fa50f367a1ef38097ee9", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "THZ1_1_R1.fastq.gz", "size": "47315077279", "date": "2023-01-27 00:41:18", "md5": "cc13640b54a668d98011330e09821aa2", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}]