Gene Regulation
Coordination between the circadian clock and androgen signaling is required to sustain rhythmic expression of Elovl3 in mouse liver

https://doi.org/10.1074/jbc.RA118.005950Get rights and content
Under a Creative Commons license
open access

ELOVL3 is a very long-chain fatty acid elongase, and its mRNA levels display diurnal rhythmic changes exclusively in adult male mouse livers. This cyclical expression of hepatic Elovl3 is potentially controlled by the circadian clock, related hormones, and transcriptional factors. It remains unknown, however, whether the circadian clock, in conjunction with androgen signaling, functions in maintaining the rhythmic expression of Elovl3 in a sexually dimorphic manner. Under either zeitgeber or circadian time, WT mouse livers exhibited a robust circadian rhythmicity in the expression of circadian clock genes and Elovl3. In contrast, male Bmal1−/− mice displayed severely weakened expression of hepatic circadian clock genes, resulting in relatively high, but nonrhythmic, Elovl3 expression levels. ChIP assays revealed that NR1D1 binds to the Elovl3 promoter upon circadian change in WT mouse livers in vivo, and a diminished binding was observed in male Bmal1−/− mouse livers. Additionally, female mouse livers exhibited constant low levels of Elovl3 expression. Castration markedly reduced Elovl3 expression levels in male mouse livers but did not disrupt circadian variation of Elovl3. Injection of female mice with 5α-dihydrotestosterone induced Elovl3 rhythmicity in the liver. In AML12 cells, 5α-dihydrotestosterone also elevated Elovl3 expression in a time-dependent manner. In contrast, flutamide efficiently attenuated this induction effect. In conclusion, a lack of either the circadian clock or androgen signaling impairs hepatic Elovl3 expression, highlighting the observation that coordination between the circadian clock and androgen signaling is required to sustain the rhythmic expression of Elovl3 in mouse liver.

androgen
circadian clock
liver
mouse
clock gene
Elovl3

Cited by (0)

This work was supported by National Natural Science Foundation of China Grants 31771301 and 31602125 (to H. C.) and 31772817 (to Y. J.), China Postdoctoral Science Foundation Grants 2017M61065 and 2018T111112 (to H. C.), Shaanxi Postdoctoral Science Foundation Grant 2017BSHEDZZ105 (to H. C.), Fundamental Research Funds for the Central Universities Grant 2452017292 (to H. C.), Scientific Research Foundation for Talents of Shaanxi Grant A279021712 (to H. C.), and Scientific Research Foundation for Talents of Northwest A&F University Grant Z11021601 (to H. C.). The authors declare that they have no conflicts of interest with the contents of this article.

This article contains Fig. S1.

6

Please note that the JBC is not responsible for the long-term archiving and maintenance of this site or any other third party hosted site.

1

Both authors contributed equally to this work.

3

Present address: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Agriculture, Kyushu University, Fukuoka, Japan.

5

The abbreviations used are:

    VLCFA

    very long-chain fatty acid

    CCG

    clock-controlled gene

    RORE

    REV-ERBs/RORs response element (RORE)

    ZT

    zeitgeber time

    CT

    circadian time

    DHT

    5α-dihydrotestosterone

    DD

    constant darkness

    LD

    light-dark

    qPCR

    quantitative real-time PCR

    ANOVA

    analysis of variance.