bims-ciryme 2021-07-18 papers

Diabetes Res Clin Pract. 2021 Jul 07. pii: S0168-8227(21)00301-6. [Epub ahead of print] 108941

Serum from type 2 diabetes patients consuming a three-meal diet resets circadian rhythms in cultured hepatocytes.

Shani Tsameret, Daniela Jakubowicz, Zohar Landau, Julio Wainstein, Tali Ganz, Itamar Raz, Nava Chapnik, Oren Froy.

AIMS: Feeding regimens alter circadian rhythms in peripheral tissues, but the mechanism is not understood. We aimed to study whether soluble factors, rather than neuronal-based communication, directly influence circadian rhythms in the liver, in response to a nutritional treatment in type 2 diabetes (T2D) patients.
METHODS: Cultured hepatocytes were treated with serum of insulin-treated T2D patients following either a three-meal diet (3Mdiet) or six-meal diet (6Mdiet) and the circadian expression of clock and metabolic genes was measured.
RESULTS: Serum of the 3Mdiet group led to increased amplitudes and daily mRNA levels of the positive limb of the circadian clock (Clock, Bmal1, Rorα). In parallel, serum of the 3Mdiet group led to the downregulation of the negative limb of the circadian clock (Cry1 and Per1), compared to both baseline and 6Mdiet. In contrast, serum of the 6Mdiet group led to a more distorted expression pattern. The catabolic genes Sirt1 and Ampk were significantly upregulated only by serum of the 3Mdiet group.
CONCLUSIONS: Our results show that serum of type 2 diabetes patients consuming the 3Mdiet contains soluble factors that reset circadian rhythms leading to an expression pattern similar to that of healthy people. This clock pattern contributes to improved glucose metabolism.

Keywords: circadian rhythms; clock; meals; metabolism; oscillation

DOI: https://doi.org/10.1016/j.diabres.2021.108941

Sci Rep. 2021 Jul 13. 11(1): 14431

Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function.

Ling-Chih Chen, Yung-Lin Hsieh, Grace Y T Tan, Tai-Yun Kuo, Yu-Chi Chou, Pang-Hung Hsu, Wendy W Hwang-Verslues.

Posttranslational modification (PTM) of core circadian clock proteins, including Period2 (PER2), is required for proper circadian regulation. PER2 function is regulated by casein kinase 1 (CK1)-mediated phosphorylation and ubiquitination but little is known about other PER2 PTMs or their interaction with PER2 phosphorylation. We found that PER2 can be SUMOylated by both SUMO1 and SUMO2; however, SUMO1 versus SUMO2 conjugation had different effects on PER2 turnover and transcriptional suppressor function. SUMO2 conjugation facilitated PER2 interaction with β-TrCP leading to PER2 proteasomal degradation. In contrast, SUMO1 conjugation, mediated by E3 SUMO-protein ligase RanBP2, enhanced CK1-mediated PER2S662 phosphorylation, inhibited PER2 degradation and increased PER2 transcriptional suppressor function. PER2 K736 was critical for both SUMO1- and SUMO2-conjugation. A PER2K736R mutation was sufficient to alter PER2 protein oscillation and reduce PER2-mediated transcriptional suppression. Together, our data revealed that SUMO1 versus SUMO2 conjugation acts as a determinant of PER2 stability and function and thereby affects the circadian regulatory system and the expression of clock-controlled genes.

DOI: https://doi.org/10.1038/s41598-021-93933-y

BMC Genomics. 2021 Jul 10. 22(1): 529

Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars.

Yanlei Yue, Ze Jiang, Enoch Sapey, Tingting Wu, Shi Sun, Mengxue Cao, Tianfu Han, Tao Li, Hai Nian, Bingjun Jiang.

BACKGROUND: In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear.
RESULTS: We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean.
CONCLUSIONS: These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.

Keywords: Circadian rhythmicity; GmFT family; J/GmELF3a; Soybean; Time-series transcriptome

DOI: https://doi.org/10.1186/s12864-021-07869-8