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Series GSE164777 Query DataSets for GSE164777
Status Public on Jan 17, 2022
Title MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary The MYC oncogene encodes for the MYC protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. MYC overexpression leads to MYC binding at active enhancers, resulting in a global transcriptional amplification of active genes. Since superenhancers are frequently dysregulated in cancer, we hypothesized that MYC preferentially invades into superenhancers and alters the cancer genome organization. To that end, we performed ChIP-seq, RNA-seq, 4C-seq and SIQHiC (Spike-in Quantitative Hi-C) on the U2OS osteosarcoma cell line with tetracycline-inducible MYC. MYC overexpression in U2OS cells modulated histone acetylation and increased MYC binding at superenhancers. SIQHiC analysis revealed increased global chromatin contact frequency, particularly at chromatin interactions connecting MYC binding sites at promoters and enhancers. Immunofluorescence staining showed that MYC molecules formed punctate foci at these transcriptionally active domains after MYC overexpression. These results demonstrate the accumulation of overexpressed MYC at promoter-enhancer hubs and suggest that MYC invades into enhancers through spatial proximity. At the same time, the increased protein-protein interactions may strengthen these chromatin interactions to increase chromatin contact frequency. CTCF siRNA knockdown in MYC overexpressed U2OS cells demonstrated that removal of architectural proteins can disperse MYC and abrogate the increase in chromatin contacts. By elucidating the chromatin landscape of MYC driven cancers, we can potentially target MYC associated chromatin interactions for cancer therapy.
 
Overall design Spike-In Quantitative Hi-C (SIQHiC), ChIP-Seq, RNA-Seq and 4C-Seq performed on 2 biological replicates of U2OS cells treated with doxycycline or vehicle (H2O) for 30h, with NIH3T3 mouse cells spiked in.
 
Contributor(s) See Y, Chen K, Fullwood MJ
Citation(s) 35115371
Submission date Jan 13, 2021
Last update date Mar 01, 2022
Contact name Melissa Jane Fullwood
E-mail(s) mfullwood@ntu.edu.sg
Organization name Nanyang Technological University
Street address 60 Nanyang Drive​​
City Singapore
ZIP/Postal code 637551
Country Singapore
 
Platforms (3)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL25431 Illumina HiSeq 4000 (Homo sapiens; Mus musculus)
Samples (28)
GSM5018573 U2OS cells - LowMYC_rep1_HiC
GSM5018574 U2OS cells - LowMYC_rep2_HiC
GSM5018575 U2OS cells - HighMYC_rep1_HiC
Relations
BioProject PRJNA691927
SRA SRP301619

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE164777_HighMYC_R1_abundance.tsv.gz 1.0 Mb (ftp)(http) TSV
GSE164777_HighMYC_R2_abundance.tsv.gz 1.0 Mb (ftp)(http) TSV
GSE164777_LowMYC_R1_abundance.tsv.gz 1.0 Mb (ftp)(http) TSV
GSE164777_LowMYC_R2_abundance.tsv.gz 1.0 Mb (ftp)(http) TSV
GSE164777_U2OS_H3K27ac_DOX+_peaks.narrowPeak.gz 2.0 Mb (ftp)(http) NARROWPEAK
GSE164777_U2OS_H3K27ac_DOX-_peaks.narrowPeak.gz 2.0 Mb (ftp)(http) NARROWPEAK
GSE164777_U2OS_MYC_DOX+_peaks.narrowPeak.gz 322.0 Kb (ftp)(http) NARROWPEAK
GSE164777_U2OS_MYC_DOX-_peaks.narrowPeak.gz 197.5 Kb (ftp)(http) NARROWPEAK
GSE164777_U2OS_merge_C-_COM.trimmed_experiment.interactions.txt.gz 718.1 Kb (ftp)(http) TXT
GSE164777_U2OS_merge_C_COM.trimmed_experiment.interactions.txt.gz 869.1 Kb (ftp)(http) TXT
GSE164777_inter_30_hi_merged.hic 3.9 Gb (ftp)(http) HIC
GSE164777_inter_30_low_1_merged_SIQHIC.hic 657.6 Mb (ftp)(http) HIC
GSE164777_inter_30_low_merged.hic 5.4 Gb (ftp)(http) HIC
GSE164777_siCTCF_merged_inter_30.hic 9.8 Gb (ftp)(http) HIC
GSE164777_siCTCF_merged_inter_30_SIQHIC.hic 980.0 Mb (ftp)(http) HIC
GSE164777_siControl_merged_inter_30.hic 8.5 Gb (ftp)(http) HIC
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Raw data are available in SRA
Processed data are available on Series record

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