Please use this identifier to cite or link to this item:
Title: MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites
Authors: See, Yi Xiang
Chen, Kaijing
Fullwood, Melissa Jane
Keywords: Science::Biological sciences::Genetics
Science::Biological sciences::Molecular biology
Issue Date: 2022
Source: See, Y. X., Chen, K. & Fullwood, M. J. (2022). MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites. Genome Research.
Project: MOE2014-T3-1-006
Journal: Genome Research
Abstract: 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.
ISSN: 1088-9051
DOI: 10.1101/gr.276313.121
Rights: This manuscript is Open Access. This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International license), as described at
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Files in This Item:
File Description SizeFormat 
Genome Res.-2022-See-gr.276313.121.pdfMain1 MBAdobe PDFView/Open
Supplemental_Materials.pdfSupplemental Materials4.17 MBAdobe PDFView/Open

Page view(s)

Updated on Jun 28, 2022


Updated on Jun 28, 2022

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.