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Comment
. 2017 Mar 23:8:14918.
doi: 10.1038/ncomms14918.

Correspondence: Reply to 'Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα'

Anton Shostak  1 , Bianca Ruppert  1 , Axel Diernfellner  1 , Michael Brunner  1
Affiliations
Comment

Correspondence: Reply to 'Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα'

Anton Shostak et al. Nat Commun. .
No abstract available

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Overexpression of MYC moderately increases REV-ERBα in U2OS cells.
(a) qPCR reevaluation of RNA expression data from Shostak et al. at two circadian time points using primers from Zhang et al. and Altman et al.. Data were normalized to GAPDH (upper row) or B2M (lower row) by ΔΔCt (n=3). (b) qPCR analysis of circadian expression profiles of indicated transcripts in synchronized U2OS t-rex tetO-MYC cells normalized to GAPDH (upper row) or B2M (lower row) (n=3). qPCR products were detected with SYBR Green, corresponding quantification with TaqMan probes is shown in Supplementary Fig. 1a. (c) Western blot analysis (upper panel) and densitometric protein quantification (lower panel) of indicated proteins in synchronized U2OS t-rex tetO-MYC cells in presence (Dox) and absence (PBS) of overexpressed MYC (n=1). Data are presented as mean±s.e.m. *P<0.05; two-way ANOVA with Bonferroni post-test.
Figure 2
Figure 2. MYC represses BMAL1 and CLOCK in absence of REV-ERBα.
(a) MYC-dependent reduction of BMAL1 and CLOCK levels in presence and absence of REV-ERBα. U2OS t-rex tetO-MYC cells were transfected with REV-ERBα or negative siRNAs as indicated. After 24 h cells were treated with doxycycline to induce MYC (MYC ox) or with PBS for control (Ctrl). Western blot analysis (left) and densitometric protein quantification (right) (n=3) are shown. *P<0.05 for Ctrl versus MYC ox; #P<0.05 for neg siRNA versus REV-ERBα siRNA by two-way ANOVA. (b) MYC-dependent repression of Bmal1 promoters with and without ROREs. Schematic of the Bmal1-luc construct showing the location of ROREs. Sequence changes inactivating ROREs are underlined (right panel). U2OS t-rex tetO-MYC cells transiently transfected with Bmal1-luc (left) or Bmal1-ΔRORE1,2-luc (right) were treated with doxycycline (MYC ox) or PBS (Ctrl) as indicated and, bioluminescence traces were recorded (n=3). Data are presented as mean±s.e.m. (c) Schematic of MYC-dependent direct and indirect repression of BMAL1.
See this image and copyright information in PMC

Comment on

  • MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells.
    Altman BJ, Hsieh AL, Sengupta A, Krishnanaiah SY, Stine ZE, Walton ZE, Gouw AM, Venkataraman A, Li B, Goraksha-Hicks P, Diskin SJ, Bellovin DI, Simon MC, Rathmell JC, Lazar MA, Maris JM, Felsher DW, Hogenesch JB, Weljie AM, Dang CV. Altman BJ, et al. Cell Metab. 2015 Dec 1;22(6):1009-19. doi: 10.1016/j.cmet.2015.09.003. Epub 2015 Sep 17. Cell Metab. 2015. PMID: 26387865 Free PMC article.

References

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