EXPERIMENT_TITLE: GSM4887090: Mutu-LCL cell line, olaparib treated, replicate 1; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: After 72 hour incubation with or without olaparib, five million cells per condition were collected for in situ Hi-C as per Rao et al. Cell 2014. Libraries of total ligation products were produced using Ultralow Library Systems V2 (Tecan Genomics, part no. 0344NB-32) as per manufacturer's protocol
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Epstein-Barr virus (EBV) establishes life-long latency in human B-cells by maintaining its chromatinized episomes within the nucleus. These circularized mini-chromosomes do not integrate into the host genome. Therefore, it is essential for EBV to organize its chromatin in a manner suitable for genomic stability, DNA replication, and efficient gene expression. Poly [ADP-ribose] polymerase 1 (PARP1) activity is significantly higher in B-cells infected with EBV than those without, and considerably higher in the transcriptionally active type III latency compared to the immunoevasive type I. In addition to its role in DNA damage response, PARP1 has been implicated in transcriptional regulation and structural maintenance of both the human and EBV genome at specific regions. To better understand PARP1's role in the regulation of the EBV episome, we have functionally characterized the effect of PARP enzymatic inhibition on total episomal structure through in situ Hi-C mapping, generating the first complete 3D structure of the EBV genome. We have also mapped intragenomic contact changes after PARP inhibition to global binding of the chromatin looping factors CTCF and cohesin across the EBV genome.  Additionally, PARP inhibition was shown to alter gene expression at the regions where chromatin looping was most effected. Finally, we have identified a novel function of PARP, which regulates cohesin complex chromatin binding. In conclusion, PARP1 inhibition does not alter the location of cohesin binding but does increase its frequency of binding at these regions. Despite this, there are fewer overall unique intragenomic interactions after PARP inhibition, while some areas have new chromatin loops not seen in the untreated EBV episome, leading us to conclude that PARP does have an essential role in the regulation of global EBV chromatin structure. The altered expression profile after the structural rearrangement induced by PARP inhibition also supports the idea that PARP1 helps maintain EBV latency programs. Overall design: HiC in Mutu I and Mutu LCL cell lines under control and olaparib-treated conditions CHIP-seq of CTCF in Mutu I and Mutu LCL cell lines with IgG control
SAMPLE_TITLE: GEO accession GSM4887090 is currently private and is scheduled to be released on Nov 05, 2021.
Pool_Member_@attributes_sample_title: GEO accession GSM4887090 is currently private and is scheduled to be released on Nov 05, 2021.
RUN_SET_RUN_Pool_Member_@attributes_sample_title: GEO accession GSM4887090 is currently private and is scheduled to be released on Nov 05, 2021.
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