До питання проблематики розвитку логістичного аутсорсингу ринку України

Genomic imprinting, the epigenetic process by which transcription occurs from a single parental allele, is believed influence social behaviours in mammals. An important social behaviour is group living, which is enriched in Eutherian mammals relative to monotremes and marsupials. Group living facilitates resource acquisition, defence of territory and co-care of young, but requires a stable social group with complex inter-individual relationships. Co-occurring with increased group living in Eutherians is an increase in the number of imprinted loci, including that spanning the maternally expressed Cdkn1c. Using a ‘loss-of-imprinting’ model of Cdkn1c (Cdkn1cBACx1), we demonstrated that two-fold over expression of Cdkn1c results in abnormal social behaviours. Although our previous work indicated that male Cdkn1cBACx1 mice were more dominant as measured by tube-test encounters with unfamiliar wild-type males. Building upon this work, using more ecologically relevant assessments of social dominance, indicated that within their normal social group, Cdkn1cBACx1 mice did not occupy higher ranking positions. Nevertheless, we find that presence of Cdkn1cBACx1 animals within a group leads to instability of the normal social hierarchy, as indicated by greater variability in social rank within the group over time and an increase in territorial behaviour in WT cage-mates. Consequently, these abnormal behaviours led to an increased incidence of fighting and wounding within the group. Taken together these data indicate that normal expression of Cdkn1c is required for maintaining stability of the social group and suggests that the acquisition of monoallelic expression of Cdkn1c may have enhanced social behaviour in Eutherian mammals to facilitate group living

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<p>Genomic imprinting, the epigenetic process by which transcription occurs from a single parental allele, is believed to influence social behaviors in mammals. An important social behavior is group living, which is enriched in Eutherian mammals relative to monotremes and marsupials. Group living facilitates resource acquisition, defense of territory and co-care of young, but requires a stable social group with complex inter-individual relationships. Co-occurring with increased group living in Eutherians is an increase in the number of imprinted loci, including that spanning the maternally expressed Cdkn1c. Using a ‘loss-of-imprinting’ model of Cdkn1c (Cdkn1c^BACx1), we demonstrated that twofold over expression of Cdkn1c results in abnormal social behaviors. Although, our previous work indicated that male Cdkn1c^BACx1 mice were more dominant as measured by tube test encounters with unfamiliar wild-type (WT) males. Building upon this work, using more ecologically relevant assessments of social dominance, indicated that within their normal social group, Cdkn1c^BACx1 mice did not occupy higher ranking positions. Nevertheless, we find that presence of Cdkn1c^BACx1 animals within a group leads to instability of the normal social hierarchy, as indicated by greater variability in social rank within the group over time and an increase in territorial behavior in WT cage-mates. Consequently, these abnormal behaviors led to an increased incidence of fighting and wounding within the group. Taken together these data indicate that normal expression of Cdkn1c is required for maintaining stability of the social group and suggests that the acquisition of monoallelic expression of Cdkn1c may have enhanced social behavior in Eutherian mammals to facilitate group living.</p

Image_3.PDF

<p>Genomic imprinting, the epigenetic process by which transcription occurs from a single parental allele, is believed to influence social behaviors in mammals. An important social behavior is group living, which is enriched in Eutherian mammals relative to monotremes and marsupials. Group living facilitates resource acquisition, defense of territory and co-care of young, but requires a stable social group with complex inter-individual relationships. Co-occurring with increased group living in Eutherians is an increase in the number of imprinted loci, including that spanning the maternally expressed Cdkn1c. Using a ‘loss-of-imprinting’ model of Cdkn1c (Cdkn1c^BACx1), we demonstrated that twofold over expression of Cdkn1c results in abnormal social behaviors. Although, our previous work indicated that male Cdkn1c^BACx1 mice were more dominant as measured by tube test encounters with unfamiliar wild-type (WT) males. Building upon this work, using more ecologically relevant assessments of social dominance, indicated that within their normal social group, Cdkn1c^BACx1 mice did not occupy higher ranking positions. Nevertheless, we find that presence of Cdkn1c^BACx1 animals within a group leads to instability of the normal social hierarchy, as indicated by greater variability in social rank within the group over time and an increase in territorial behavior in WT cage-mates. Consequently, these abnormal behaviors led to an increased incidence of fighting and wounding within the group. Taken together these data indicate that normal expression of Cdkn1c is required for maintaining stability of the social group and suggests that the acquisition of monoallelic expression of Cdkn1c may have enhanced social behavior in Eutherian mammals to facilitate group living.</p

Image_2.PDF

<p>Genomic imprinting, the epigenetic process by which transcription occurs from a single parental allele, is believed to influence social behaviors in mammals. An important social behavior is group living, which is enriched in Eutherian mammals relative to monotremes and marsupials. Group living facilitates resource acquisition, defense of territory and co-care of young, but requires a stable social group with complex inter-individual relationships. Co-occurring with increased group living in Eutherians is an increase in the number of imprinted loci, including that spanning the maternally expressed Cdkn1c. Using a ‘loss-of-imprinting’ model of Cdkn1c (Cdkn1c^BACx1), we demonstrated that twofold over expression of Cdkn1c results in abnormal social behaviors. Although, our previous work indicated that male Cdkn1c^BACx1 mice were more dominant as measured by tube test encounters with unfamiliar wild-type (WT) males. Building upon this work, using more ecologically relevant assessments of social dominance, indicated that within their normal social group, Cdkn1c^BACx1 mice did not occupy higher ranking positions. Nevertheless, we find that presence of Cdkn1c^BACx1 animals within a group leads to instability of the normal social hierarchy, as indicated by greater variability in social rank within the group over time and an increase in territorial behavior in WT cage-mates. Consequently, these abnormal behaviors led to an increased incidence of fighting and wounding within the group. Taken together these data indicate that normal expression of Cdkn1c is required for maintaining stability of the social group and suggests that the acquisition of monoallelic expression of Cdkn1c may have enhanced social behavior in Eutherian mammals to facilitate group living.</p

Peg3 Deficiency Results in Sexually Dimorphic Losses and Gains in the Normal Repertoire of Placental Hormones.

Hormones from the fetally derived placenta signal to the mother throughout pregnancy to ensure optimal fetal growth and prepare the mother for her new role in nurturing her offspring. Through evolution, placental hormones have under gone remarkable diversification and species-specific expansions thought to be due to constant rebalancing of resource allocation between mother and offspring. Genomic imprinting, an epigenetic process in which parental germlines silence genes in the offspring, is thought to be the physical embodiment of a second conflicting interest, between the male and female mammal. Several genes silenced by paternal imprints normally function to limit the placental endocrine lineages of the mouse placenta. We hypothesized that paternal imprinting has adapted to overcome the rapid evolution of placental hormone gene families by directly regulating the lineages that express these hormones rather than individual hormones. This predicts the existence of genes maternally silenced in the offspring counteracting the influence of the paternal imprint. Here we report on the consequences of loss of function of Paternally expressed gene 3 (Peg3), on placental endocrine lineages. Mutant male placenta displayed a marked loss of the spongiotrophoblast, a key endocrine lineage of the placenta, and the glycogen cell lineage alongside reduced stores of placental glycogen and changes in expression of the normal repertoire of placental hormones. Peg3 is known to transcriptionally repress placental hormone genes. Peg3 consequently both positively and negatively regulates placental hormones through two independent and opposing mechanisms. Female placenta showed moderate response to loss of Peg3 with minor alterations to the junctional zone lineages and few changes in gene expression. These data highlight the important fact that female placenta compensate for the loss of Peg3 better than male placenta. This work lends further support to our novel hypothesis that the parental genomes are competing over the endocrine function of the mouse placenta and further suggests that a conflict between males and females begins in utero

Peg3 Deficiency Results in Sexually Dimorphic Losses and Gains in the Normal Repertoire of Placental Hormones.

Hormones from the fetally derived placenta signal to the mother throughout pregnancy to ensure optimal fetal growth and prepare the mother for her new role in nurturing her offspring. Through evolution, placental hormones have under gone remarkable diversification and species-specific expansions thought to be due to constant rebalancing of resource allocation between mother and offspring. Genomic imprinting, an epigenetic process in which parental germlines silence genes in the offspring, is thought to be the physical embodiment of a second conflicting interest, between the male and female mammal. Several genes silenced by paternal imprints normally function to limit the placental endocrine lineages of the mouse placenta. We hypothesized that paternal imprinting has adapted to overcome the rapid evolution of placental hormone gene families by directly regulating the lineages that express these hormones rather than individual hormones. This predicts the existence of genes maternally silenced in the offspring counteracting the influence of the paternal imprint. Here we report on the consequences of loss of function of Paternally expressed gene 3 (Peg3), on placental endocrine lineages. Mutant male placenta displayed a marked loss of the spongiotrophoblast, a key endocrine lineage of the placenta, and the glycogen cell lineage alongside reduced stores of placental glycogen and changes in expression of the normal repertoire of placental hormones. Peg3 is known to transcriptionally repress placental hormone genes. Peg3 consequently both positively and negatively regulates placental hormones through two independent and opposing mechanisms. Female placenta showed moderate response to loss of Peg3 with minor alterations to the junctional zone lineages and few changes in gene expression. These data highlight the important fact that female placenta compensate for the loss of Peg3 better than male placenta. This work lends further support to our novel hypothesis that the parental genomes are competing over the endocrine function of the mouse placenta and further suggests that a conflict between males and females begins in utero

Dosage-sensitivity of imprinted genes expressed in the brain: 15q11–q13 and neuropsychiatric illness

Imprinted genes, those genes subject to parent-of-origin-specific epigenetic marking resulting in monoallelic parent-specific expression, are sensitive to subtle changes in expression dosage. This has been illustrated in a number of experimental models and the fact that both decreased (or complete loss) and increased imprinted gene expression can lead to human diseases. In the present paper, we discuss the consequence of increased dosage of imprinted genes for brain function, focusing on the PWS (Prader–Willi syndrome) locus on human chromosome 15q11–q13 and how predicted increases in dosage of maternally expressed imprinted genes from this interval are associated with a higher risk of developing psychotic illness. The evidence for this comes from individuals with PWS itself and also non-syndromic cases of psychosis in carriers of a maternally derived copy number variant spanning this locus. Of the known imprinted genes in this region, the prime candidate is maternally expressed UBE3A, which encodes E6-AP (E6-associated protein) ubiquitin ligase and has an influence on a number of important neurotransmitter systems. Furthermore, these findings point to the fact that brain function is exquisitely sensitive to both decreases and increases in the expression of imprinted genes