FUBP1 and FUBP2 enforce distinct epigenetic setpoints for MYC expression in primary single murine cells

Ying Zheng, Wendy Dubois, Craig Benham, Eric Batchelor, David Levens

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Physiologically, MYC levels must be precisely set to faithfully amplify the transcriptome, but in cancer MYC is quantitatively misregulated. Here, we study the variation of MYC amongst single primary cells (B-cells and murine embryonic fibroblasts, MEFs) for the repercussions of variable cellular MYC-levels and setpoints. Because FUBPs have been proposed to be molecular “cruise controls” that constrain MYC expression, their role in determining basal or activated MYC-levels was also examined. Growing cells remember low and high-MYC setpoints through multiple cell divisions and are limited by the same expression ceiling even after modest MYC-activation. High MYC MEFs are enriched for mRNAs regulating inflammation and immunity. After strong stimulation, many cells break through the ceiling and intensify MYC expression. Lacking FUBPs, unstimulated MEFs express levels otherwise attained only with stimulation and sponsor MYC chromatin changes, revealed by chromatin marks. Thus, the FUBPs enforce epigenetic setpoints that restrict MYC expression.

Original languageEnglish (US)
Article number545
JournalCommunications biology
Issue number1
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
We thank Dr. Ferenc Livak in Flow Cytometry Core Facility (NCI, CCR) for assistance with the flow cytometry and sorting. We thank the sequencing facility (NCI, CCR) for assistance with next-generation sequencing. We thank the ENCODE Consortium and the Bing Ren lab (UCSD) generating the ENCSR030BUT data set. This work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research.

Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.


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