Peg3 (paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein. This gene plays important roles in controlling fetal growth rates and nurturing behaviors. In the current study, a new mutant mouse model has been generated to further characterize the functions of this DNA-binding protein. Besides known phenotypes, this new mutant model also revealed potential roles of Peg3 in mammalian reproduction. Female heterozygotes produce a much smaller number of mature oocytes than the wild-type littermates, resulting in reduced litter sizes. According to genome-wide expression analyses, several placenta-specific gene families are de-repressed in the brain of Peg3 heterozygous embryos, including prolactin, cathepsin and carcinoembryonic antigen cell adhesion molecule (Ceacam) families. The observed de-repression is more pronounced in females than in males. The de-repression of several members of these gene families is observed even in the adult brain, suggesting potential defects in epigenetic setting of the placenta-specific gene families in the Peg3 mutants. Overall, these results indicate that Peg3 likely controls the transcription of several placenta-specific gene families, and further suggest that this predicted transcriptional control by Peg3 might be mediated through unknown epigenetic mechanisms.
The imprinting of the mouse Peg3 domain is controlled through a 4-kb genomic region encompassing the bidirectional promoter and 1 st exons of Peg3 and Usp29. In the current study, this ICR was inverted to test its orientation dependency for the transcriptional and imprinting control of the Peg3 domain. The inversion resulted in the exchange of promoters and 1 st exons between Peg3 and Usp29. Paternal transmission of this inversion caused 10-fold down-regulation of Peg3 and 2-fold up-regulation of Usp29 in neonatal heads, consistent with its original promoter strength in each direction. The paternal transmission also resulted in reduced body size among the animals, which was likely contributed by the dramatic down-regulation of Peg3. Transmission through either allele caused no changes in the DNA methylation and imprinting status of the Peg3 domain except that Zfp264 became bi-allelic through the maternal transmission. Overall, the current study suggests that the orientation of the Peg3-ICR may play no role in its allele-specific DNA methylation, but very critical for the transcriptional regulation of the entire imprinted domain.
In mammals, genomic imprinting has evolved as a dosage-controlling mechanism for a subset of genes that play critical roles in their unusual reproduction scheme involving viviparity and placentation. As such, many imprinted genes are highly expressed in sex-specific reproductive organs. In the current study, we sought to test whether imprinted genes are differentially expressed between the two sexes. According to the results, the expression levels of the following genes differ between the two sexes of mice: Peg3, Zim1, Igf2, H19 and Zac1. The expression levels of these imprinted genes are usually greater in males than in females. This bias is most obvious in the developing brains of 14.5-dpc embryos, but also detected in the brains of postnatal-stage mice. However, this sexual bias is not obvious in 10.5-dpc embryos, a developmental stage before the sexual differentiation. Thus, the sexual bias observed in the imprinted genes is most likely attributable by gonadal hormones rather than by sex chromosome complement. Overall, the results indicate that several imprinted genes are sexually different in terms of their expression levels, and further suggest that the transcriptional regulation of these imprinted genes may be influenced by unknown mechanisms associated with sexual differentiation.
A protocol has been developed for plant regeneration from encapsulated nodal segments of Tylophora indica. Nodal segments collected from a 2-year-old plant were encapsulated in calcium alginate beads. The best gel complex was achieved using 3% (w/v) sodium alginate and 100 mM CaCl 2 .2H 2 O. The maximum frequency (91%) of conversion of encapsulated beads into plantlets was achieved on Murashige and Skoog (MS) medium containing 2.5 µM 6-benzyladenine (BA) and 0.5 µM ␣-naphthalene acetic acid (NAA) after 6 weeks of culture. Encapsulated nodal segments stored at 4°C for 1 -8 weeks also showed successful conversion, followed by development into complete plantlets when returned to regeneration medium. Conversion of encapsulated nodal segment into plantlets also occurred when the calcium alginate beads were sown directly into Soilrite TM moistened with 1 ⁄ 2MS salts. Plants regenerated from encapsulated nodal segments could be hardened, acclimatised and established in soil, with a success rate of 90%. Encapsulation of vegetative propagules in calcium alginate beads could be useful for the exchange, storage and micropropagation of germplasm of this endangered medicinal plant.
Pendimethalin (PM) is a dinitroaniline herbicide extensively applied against the annual grasses and broad-leaved weeds. There is no report available on PM-induced low-dose genotoxicity in human primary cells and in vivo test models. Such data gap has prompted us to evaluate the genotoxic potential of PM in human lymphocytes and rats. PM selectively binds in the minor groove of DNA by forming covalent bonds with G and C nitrogenous bases, as well as with the ribose sugar. PM induces micronucleus formation (MN) in human lymphocytes, indicating its clastogenic potential. Comet assay data showed 35.6-fold greater DNA damage in PM (200 μM)-treated human lymphocytes. Rat bone-marrow cells, at the highest dose of 50 mg/kg b w/day of PM also exhibited 10.5-fold greater DNA damage. PM at 200 μM and 50 mg/kg b w/day induces 193.4 and 229% higher reactive oxygen species generation in human lymphocytes and rat bone-marrow cells. PM-treated human lymphocytes and rat bone-marrow cells both showed dysfunction of mitochondrial membrane potential (ΔΨ ). PM exposure results in the appearance of 72.2 and 35.2% sub-G apoptotic peaks in human lymphocytes and rat bone-marrow cells when treated with 200 μM and 50 mg/kg b w/day of PM. Rats exposed to PM also showed imbalance in antioxidant enzymes and histological pathology. Overall, our data demonstrated the genotoxic and apoptotic potentials of PM in human and animal test models.
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