Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

MYC overexpression leads to increased chromatin interactions at superenhancers and c-Myc binding sites

View ORCID ProfileYi Xiang See, Kaijing Chen, View ORCID ProfileMelissa J. Fullwood
doi: https://doi.org/10.1101/2021.01.04.425344
Yi Xiang See
1School of Biological Sciences, Nanyang Technological University, Singapore
2Cancer Science Institute of Singapore, National University of Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yi Xiang See
Kaijing Chen
1School of Biological Sciences, Nanyang Technological University, Singapore
2Cancer Science Institute of Singapore, National University of Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melissa J. Fullwood
1School of Biological Sciences, Nanyang Technological University, Singapore
2Cancer Science Institute of Singapore, National University of Singapore
3Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Melissa J. Fullwood
  • For correspondence: mfullwood@ntu.edu.sg
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The MYC oncogene encodes for the c-Myc protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. There have been many difficulties in targeting c-Myc, due to its complex network of regulators and the unstructured nature of its protein. Thus, we are interested in looking at the downstream cancer-specific functions of c-Myc. Overexpression of MYC leads to c-Myc binding at active enhancers, resulting in a global transcriptional amplification of active genes. However, the mechanism underlying this c-Myc enhancer invasion has not been well studied. 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 c-Myc binding at superenhancers. SIQHiC analysis revealed increased global chromatin contact frequency, particularly at chromatin interactions connecting c-Myc binding sites. Our results suggest that c-Myc molecules are recruited to and accumulates within zones of high transcription activity, binding first at stable promoter binding sites at low expression levels, then at superenhancer binding sites when overexpressed. At the same time, the recruitment of c-Myc and other transcription factors may stabilize chromatin interactions to increase chromatin contact frequency. The accumulation of c-Myc at cancer-type specific superenhancers may then drive the expression of interacting oncogenes that each cancer is highly reliant on. By elucidating the chromatin landscape of c-Myc driven cancers, we can potentially target these chromatin interactions for cancer therapy, without affecting physiological c-Myc signaling.

Competing Interest Statement

M.J.F declares two patents on methodologies related to ChIA-PET. No other conflicts of interest are declared.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 05, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
MYC overexpression leads to increased chromatin interactions at superenhancers and c-Myc binding sites
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
MYC overexpression leads to increased chromatin interactions at superenhancers and c-Myc binding sites
Yi Xiang See, Kaijing Chen, Melissa J. Fullwood
bioRxiv 2021.01.04.425344; doi: https://doi.org/10.1101/2021.01.04.425344
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
MYC overexpression leads to increased chromatin interactions at superenhancers and c-Myc binding sites
Yi Xiang See, Kaijing Chen, Melissa J. Fullwood
bioRxiv 2021.01.04.425344; doi: https://doi.org/10.1101/2021.01.04.425344

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2430)
  • Biochemistry (4791)
  • Bioengineering (3332)
  • Bioinformatics (14677)
  • Biophysics (6637)
  • Cancer Biology (5168)
  • Cell Biology (7425)
  • Clinical Trials (138)
  • Developmental Biology (4365)
  • Ecology (6873)
  • Epidemiology (2057)
  • Evolutionary Biology (9918)
  • Genetics (7346)
  • Genomics (9527)
  • Immunology (4554)
  • Microbiology (12684)
  • Molecular Biology (4945)
  • Neuroscience (28325)
  • Paleontology (199)
  • Pathology (808)
  • Pharmacology and Toxicology (1391)
  • Physiology (2024)
  • Plant Biology (4497)
  • Scientific Communication and Education (977)
  • Synthetic Biology (1299)
  • Systems Biology (3914)
  • Zoology (726)