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Communication

Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers

1
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
2
Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA
3
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama 230-0045, Japan
4
RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama 230-0045, Japan
5
Preventive Medicine and Applied Genomics Unit, RIKEN Advanced Center for Computing and Communication, Yokohama 230-0045, Japan
6
Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
*
Author to whom correspondence should be addressed.
Genes 2018, 9(6), 270; https://doi.org/10.3390/genes9060270
Received: 20 March 2018 / Revised: 14 May 2018 / Accepted: 15 May 2018 / Published: 23 May 2018
(This article belongs to the Section Molecular Genetics and Genomics)
In Metazoans, transcription of most genes is driven by the use of multiple alternative promoters. Although the precise regulation of alternative promoters is important for proper gene expression, the mechanisms that mediates their differential utilization remains unclear. Here, we investigate how the two alternative promoters (P1, P2) that drive MYC expression are regulated. We find that P1 and P2 can be differentially regulated across cell-types and that their selective usage is largely mediated by distal regulatory sequences. Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation. View Full-Text
Keywords: alternative promoters; enhancer-promoter specificity; MYC; Wnt-responsive enhancers alternative promoters; enhancer-promoter specificity; MYC; Wnt-responsive enhancers
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MDPI and ACS Style

Bardales, J.A.; Wieser, E.; Kawaji, H.; Murakawa, Y.; Darzacq, X. Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers. Genes 2018, 9, 270. https://doi.org/10.3390/genes9060270

AMA Style

Bardales JA, Wieser E, Kawaji H, Murakawa Y, Darzacq X. Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers. Genes. 2018; 9(6):270. https://doi.org/10.3390/genes9060270

Chicago/Turabian Style

Bardales, Jorge A., Evin Wieser, Hideya Kawaji, Yasuhiro Murakawa, and Xavier Darzacq. 2018. "Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers" Genes 9, no. 6: 270. https://doi.org/10.3390/genes9060270

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