Survey of activation-induced genome architecture reveals a novel enhancer of Myc

Wing Fuk Chan, Hannah D. Coughlan, Michelle Ruhle, Nadia Iannarella, Carolina Alvarado, Joanna R. Groom, Christine R. Keenan, Andrew J. Kueh, Adam K. Wheatley, Gordon K. Smyth, Rhys S. Allan, Timothy M. Johanson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The transcription factor Myc is critically important in driving cell proliferation, a function that is frequently dysregulated in cancer. To avoid this dysregulation Myc is tightly controlled by numerous layers of regulation. One such layer is the use of distal regulatory enhancers to drive Myc expression. Here, using chromosome conformation capture to examine B cells of the immune system in the first hours after their activation, we reveal a previously unidentified enhancer of Myc. The interactivity of this enhancer coincides with a dramatic, but discrete, spike in Myc expression 3 h post-activation. However, genetic deletion of this region, has little impact on Myc expression, Myc protein level or in vitro and in vivo cell proliferation. Examination of the enhancer deleted regulatory landscape suggests that enhancer redundancy likely sustains Myc expression. This work highlights not only the importance of temporally examining enhancers, but also the complexity and dynamics of the regulation of critical genes such as Myc.

Original languageEnglish
Pages (from-to)345-357
Number of pages13
JournalImmunology and Cell Biology
Volume101
Issue number4
DOIs
Publication statusPublished - Apr 2023
Externally publishedYes

Keywords

  • B cell activation
  • B lymphocytes
  • chromosome conformation capture
  • differential enhancer usage
  • enhancer redundancy
  • Myc

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