Spatio-temporal expression profile of sirtuins during aging of the annual fish Nothobranchius furzeri

Erosion of the epigenetic DNA methylation landscape is a widely recognized hallmark of aging. Emerging advances in high throughput sequencing techniques, in particular DNA methylation data analysis, have resulted in the establishment of precise human and murine age prediction tools. In vertebrates, methylation of cytosine at the C5 position of CpG dinucleotides is executed by DNA methyltransferases (DNMTs) whereas the process of enzymatic demethylation is highly dependent on the activity of the ten-eleven translocation methylcytosine dioxygenase (TET) family of enzymes. Here, we report the identification of the key players constituting the DNA methylation machinery in the short-lived teleost aging model Nothobranchius furzeri. We present a comprehensive spatio-temporal expression profile of the methylation-associated enzymes from embryogenesis into late adulthood, thereby covering the complete killifish life cycle. Data mining of the N. furzeri genome produced five dnmt gene family orthologues corresponding to the mammalian DNMTs (DNMT1, 2, 3A, and 3B). Comparable to other teleost species, N. furzeri harbors multiple genomic copies of the de novo DNA methylation subfamily. A related search for the DNMT1 recruitment factor UHRF1 and TET family members resulted in the identification of N. furzeri uhrf1, tet1, tet2, and tet3. Phylogenetic analysis revealed high cross-species similarity on the amino acid level of all individual dnmts, tets, and uhrf1, emphasizing a high degree of functional conservation. During early killifish development all analyzed dnmts and tets showed a similar expression profile characterized by a strong increase in transcript levels after fertilization, peaking either at embryonic day 6 or at the black eye stage of embryonic development. In adult N. furzeri, DNA methylation regulating enzymes showed a ubiquitous tissue distribution. Specifically, we observed an age-dependent downregulation of dnmts, and to some extent uhrf1, which correlated with a significant decrease in global DNA methylation levels in the aging killifish liver and muscle. The age-dependent DNA methylation profile and spatio-temporal expression characteristics of its enzymatic machinery reported here may serve as an essential platform for the identification of an epigenetic aging clock in the new vertebrate model system N. furzeri.

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Temporal expression profile of CXC chemokines in serum of patients with spinal cord injury

Neurochemistry International ◽

10.1016/j.neuint.2013.07.012 ◽

2013 ◽

Vol 63 (5) ◽

pp. 363-367 ◽

Cited By ~ 14

Author(s):

Gholamhossein Hassanshahi ◽

Masoud Amin ◽

Anandakumar Shunmugavel ◽

Reza Vazirinejad ◽

Alireza Vakilian ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Expression Profile ◽

Temporal Expression ◽

Temporal Expression Profile ◽

Cord Injury

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Insertional mutagenesis in PLNR9C transgenic mouse: a case report and a review of the literature on cardiac-specific transgenic expression

10.1101/075671 ◽

2016 ◽

Author(s):

Alexander Kraev

Keyword(s):

Expression Profile ◽

Insertional Mutagenesis ◽

Cardiac Development ◽

Integration Site ◽

Premature Death ◽

Temporal Expression ◽

Transgenic Expression ◽

Temporal Expression Profile ◽

Regulatory Circuit ◽

Non Coding Rna

AbstractA mouse line with heterozygous transgenic expression of phospholamban carrying a substitution of cysteine for arginine 9 (PLNR9C) under the control of α-myosin heavy chain (αMHC) promoter features dilated cardiomyopathy, heart failure and premature death. In this line the transgenic array of 13 PLNR9C expression cassettes, arranged in a head-to-tail tandem orientation, has integrated into the homologous genomic site, the bi-directional promoter of the αMHC (Myh6) gene and the gene for the regulatory non-coding RNA Myheart (Mhrt), both of which are involved in the execution of the α/β MHC switch during cardiac development and pathology. PLNR9C overexpression is evident at the age of 1 month but declines dramatically along with a less pronounced concomitant decline of the resident PLN expression, until the animals die. Expression of the non-coding RNA Mhrt in PLNR9C mice also exhibits a profound deregulation, despite the presence of the second, intact allele. Hence the mouse strain does not faithfully model a human PLNR9C heterozygote, wherein both the mutant and the wildtype PLN alleles have, in all likelihood, the same temporal expression profile. The intricate regulatory circuit of the α/β MHC switch, involving the non-coding RNA Mhrt, was described in detail only recently, and since publications about αMHC-driven transgenes rarely contain the definition of the transgene integration site or temporal expression profile, it is suggested that some of the pathological phenomena attributed to expression of αMHC-driven transgenes may have an alternative explanation.

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