Survey of activation-induced genome architecture reveals a novel enhancer of Myc
- Author(s)
- Chan, WF; Coughlan, HD; Ruhle, M; Iannarella, N; Alvarado, C; Groom, JR; Keenan, CR; Kueh, AJ; Wheatley, AK; Smyth, GK; Allan, RS; Johanson, TM;
- Journal Title
- Immunology & Cell Biology
- Publication Type
- epub ahead of print
- 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.
- Publisher
- Wiley
- Keywords
- B cell activation; B lymphocytes; Myc; chromosome conformation capture; differential enhancer usage; distal enhancers; enhancer redundancy; in situ HiC
- Research Division(s)
- Bioinformatics; Immunology; Blood Cells And Blood Cancer
- PubMed ID
- 36710659
- Publisher's Version
- https://doi.org/10.1111/imcb.12626
- Open Access at Publisher's Site
https://doi.org/10.1111/imcb.12626- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-17 11:09:07
Last Modified: 2023-03-17 11:11:10