The Experts below are selected from a list of 164691 Experts worldwide ranked by ideXlab platform
Joomyeong Kim - One of the best experts on this subject based on the ideXlab platform.
-
PEG3 controls lipogenesis through acly
PLOS ONE, 2021Co-Authors: Subash Ghimire, Joomyeong KimAbstract:PEG3 (Paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein that is a well-known transcriptional repressor. Previous studies have shown that the mutant phenotypes of PEG3 are associated with the over-expression of genes involved in lipid metabolism. In the current study, we investigated four potential downstream genes of PEG3, which were identified through ChIP-seq data: Acly, Fasn, Idh1, and Hmgcr. In vivo binding of PEG3 to the promoter region of these key genes involved in lipogenesis was subsequently confirmed through individual ChIP experiments. We observed the opposite response of Acly expression levels against the variable gene dosages of PEG3, involving 0x, 1x, and 2x PEG3. This suggests the transcriptional repressor role of PEG3 in the expression levels of Acly. Another set of analyses showed a sex-biased response in the expression levels of Acly, Fasn, and Idh1 against 0x PEG3 with higher levels in female and lower levels in male mammary glands. These results overall highlight that PEG3 may be involved in regulating the expression levels of several key genes in adipogenesis.
-
evolution patterns of PEG3 and h19 icr
Genomics, 2019Co-Authors: Joomyeong KimAbstract:Abstract Mammalian imprinted domains are regulated through small genomic regions termed Imprinting Control Regions (ICRs). In the current study, the evolution patterns of the ICRs of PEG3 and H19-imprinted domains were analyzed using the genomic sequences derived from a large number of mammals. The results indicated that multiple YY1 and CTCF binding sites are localized within the PEG3 and H19-ICR in all the mammals tested. The numbers of YY1 and CTCF binding sites are variable among individual species, yet positively correlate with the presence of tandem repeats within the PEG3 and H19-ICRs. Thus, multiple YY1 and CTCF binding sites within the respective ICRs may have been maintained through tandem repeats/duplications. The unit lengths of tandem repeats are also non-random and locus-specific, 140 and 400 bp for the PEG3 and H19-ICRs. Overall, both PEG3 and H19-ICRs may have co-evolved with two unique features, multiple transcription factor binding sites and tandem repeats.
-
trans allelic mutational effects at the PEG3 imprinted locus
PLOS ONE, 2018Co-Authors: Corey L Bretz, Joomyeong KimAbstract:How one allele interacts with the other for the function of a gene is not well understood. In this study, we tested potential allelic interaction at the PEG3 imprinted locus with several mutant alleles targeting an Imprinting Control Region, the PEG3-DMR. According to the results, maternal deletion of the PEG3-DMR resulted in 2-fold up-regulation of two paternally expressed genes, PEG3 and Usp29. These trans-allelic mutational effects were observed consistently throughout various tissues with different developmental stages. These effects were also associated mainly with the genetic manipulation of the PEG3-DMR, but not with the other genomic changes within the PEG3 locus. The observed trans-allelic effects were unidirectional with the maternal influencing the paternal allele, but not with the opposite direction. Overall, the observed mutational effects suggest the presence of previously unrecognized trans-allelic regulation associated with the PEG3-DMR.
-
oxytocin receptor is regulated by PEG3
PLOS ONE, 2018Co-Authors: Wesley D. Frey, Kaustubh Sharma, Terri L Cain, Katsuhiko Nishimori, Ryoichi Teruyama, Joomyeong KimAbstract:Mouse PEG3 encodes a DNA-binding protein involved in the milk letdown process. In the current study, we tested whether PEG3 controls the expression of the oxytocin receptor gene. According to the results, PEG3 directly binds to a genomic region within the 3rd exon of Oxtr, which contains a DNA-binding motif for PEG3. In nursing female mice, removal of PEG3 resulted in the increased expression of Oxtr in mammary epithelial cells and also in the hypothalamus. This suggests a repressor role of PEG3 in the expression of Oxtr in these tissues. Overall, this study suggests that PEG3 may function as a direct transcriptional regulator for Oxtr expression that acts to moderate the milk letdown process.
-
allele and dosage specificity of the PEG3 imprinted domain
PLOS ONE, 2018Co-Authors: Corey L Bretz, Wesley D. Frey, Ryoichi Teruyama, Joomyeong KimAbstract:The biological impetus for gene dosage and allele specificity of mammalian imprinted genes is not fully understood. To address this, we generated and analyzed four sets of mice from a single breeding scheme with varying allelic expression and gene dosage of the PEG3 domain. The mutants with abrogation of the two paternally expressed genes, PEG3 and Usp29, showed a significant decrease in growth rates for both males and females, while the mutants with biallelic expression of PEG3 and Usp29 resulted in an increased growth rate of female mice only. The mutant cohort with biallelic expression of PEG3 and Usp29 tended to have greater numbers of pups compared to the other genotypes. The mutants with switched active alleles displayed overall similar phenotypes to the wild type, but did show some differences in gene expression, suggesting potential non-redundant roles contributed by the maternal and paternal alleles. Overall, this study demonstrates a novel in vivo approach to investigate the allele and dosage specificity of mammalian imprinted domains.
David Sassoon - One of the best experts on this subject based on the ideXlab platform.
-
elucidating a role for pw1 PEG3 in placenta vascular formation
Archives of Cardiovascular Diseases Supplements, 2020Co-Authors: M Valente, Giovanna Marazzi, David Sassoon, S Turoczi, P Kantane, Jeansebastien HulotAbstract:Introduction Pw1/PEG3 is a parentally imprinted gene unique to placental mammals, suggesting a specific role in the placenta. Although Pw1/PEG3 is highly expressed in the placenta, the effects of a loss of function during placental development have not been well characterized. Objective To determine Pw1/PEG3 function during placental vascular formation as well as placental remodeling and how this impacts fetal intra-uterine growth in response to hypoxia. Method A comprehensive study was performed in order to analyze the placental phenotype: at the macroscopic (weight), histological (layers size and composition) and cellular (isolation of specific cell populations) levels. The functional impact of the vascular alteration of the Pw1KO placenta was accessed by the study of placental ability to remodel under hypoxia conditions. Results We observe that the Pw1/PEG3 is highly expressed in the placental labyrinth zone, i.e. fetal capillaries and syncytiotrophoblast cells, which is the site for fetal-maternal exchange. The mutant placenta displayed an overall lower weight and size coupled with an increase in endothelial and stromal cells and a decrease in pericytes, leading to an altered vascular structure. In order to determine if this altered vascular in the mutant placenta also had a functional impact, we placed pregnant dames in 10% O2 (hypoxic) environment during late fetal development. We observed that Pw1/PEG3 mutants exhibit significantly smaller placentas and embryos with asymmetric intrauterine growth restrictions as compared to wildtypes. These results demonstrate that Pw1/PEG3 is required to regulate placental plasticity in response to environmental challenges, which are critical for fetal and neonatal health, through the establishment of a functional labyrinth vascular network. Conclusion The loss of Pw1/PEG3 function impairs the development of the vascular network in the labyrinth layer and governs placental remodeling in response to hypoxia.
-
expression analysis of the stem cell marker pw1 PEG3 reveals a cd34 negative progenitor population in the hair follicle
Stem Cells, 2017Co-Authors: Vanessa Besson, Giovanna Marazzi, Sergiy Kyryachenko, Peggy Janich, Salvador Aznar Benitah, David SassoonAbstract:Pw1/PEG3 is a parentally imprinted gene expressed in adult stem cells in every tissue thus far examined including the stem cells of the hair follicle. Using a Pw1/PEG3 reporter mouse, we carried out a detailed dissection of the stem cells in the bulge, which is a major stem cell compartment of the hair follicle in mammalian skin. We observed that PW1/PEG3 expression initiates upon placode formation during fetal development, coincident with the establishment of the bulge stem cells. In the adult, we observed that PW1/PEG3 expression is found in both CD34+ and CD34- populations of bulge stem cells. We demonstrate that both populations can give rise to new hair follicles, reconstitute their niche, and self-renew. These results demonstrate that PW1/PEG3 is a reliable marker of the full population of follicle stem cells and reveal a novel CD34- bulge stem-cell population. Stem Cells 2017;35:1015-1027.
-
a novel mutant allele of pw1 PEG3 does not affect maternal behavior or nursing behavior
PLOS Genetics, 2016Co-Authors: Annelyse Denizot, Giovanna Marazzi, Rosa Maria Correra, Alessia Mazzola, Vanessa Besson, Izolina Lopes, Jeanremy Courbard, David SassoonAbstract:Parental imprinting is a mammalian-specific form of epigenetic regulation in which one allele of a gene is silenced depending on its parental origin. Parentally imprinted genes have been shown to play a role in growth, metabolism, cancer, and behavior. Although the molecular mechanisms underlying parental imprinting have been largely elucidated, the selective advantage of silencing one allele remains unclear. The mutant phenotype of the imprinted gene, Pw1/PEG3, provides a key example to illustrate the hypothesis on a coadaptation between mother and offspring, in which Pw1/PEG3 is required for a set of essential maternal behaviors, such as nursing, nest building, and postnatal care. We have generated a novel Pw1/PEG3 mutant allele that targets the last exon for the PW1 protein that contains >90% of the coding sequence resulting in a loss of Pw1/PEG3 expression. In contrast to previous reports that have targeted upstream exons, we observe that maternal behavior and lactation are not disrupted upon loss of Pw1/PEG3. Both paternal and homozygous Pw1/PEG3 mutant females nurse and feed their pups properly and no differences are detected in either oxytocin neuron number or oxytocin plasma levels. In addition, suckling capacities are normal in mutant pups. Consistent with previous reports, we observe a reduction of postnatal growth. These results support a general role for Pw1/PEG3 in the regulation of body growth but not maternal care and lactation.
-
PW1/PEG3 expression regulates key properties that determine mesoangioblast stem cell competence
Nature Communications, 2015Co-Authors: Chiara Bonfanti, Stefania Antonini, Sara Benedetti, Rossana Tonlorenzi, Giuliana Rossi, Francesco Saverio-tedesco, Monica Giannotta, Giovanna Marazzi, Elisabetta Dejana, David SassoonAbstract:Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/PEG3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/PEG3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/PEG3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibres through the modulation of the junctional adhesion molecule-A. We conclude that PW1/PEG3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/PEG3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
-
pw1 PEG3 expression regulates key properties that determine mesoangioblast stem cell competence
Nature Communications, 2015Co-Authors: Chiara Bonfanti, Stefania Antonini, Sara Benedetti, Francesco Saverio Tedesco, Rossana Tonlorenzi, Giuliana Rossi, Monica Giannotta, Giovanna Marazzi, Elisabetta Dejana, David SassoonAbstract:Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/PEG3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/PEG3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/PEG3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibres through the modulation of the junctional adhesion molecule-A. We conclude that PW1/PEG3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/PEG3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
Takashi Kohda - One of the best experts on this subject based on the ideXlab platform.
-
tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line
Genes to Cells, 2001Co-Authors: Takashi Kohda, Shin Kobayashi, Kohzo Aisaka, Yoshimi Kuroiwa, Akio Asai, Goro Nagashima, Michihiro C Yoshida, Yasumitsu Kondo, Naoto KagiyamaAbstract:Background Mouse imprinted gene PEG3 encodes a large C2H2 type zinc finger protein with unique characteristics. PEG3 knockout mice were found to show an impairment in maternal behaviour of the adult female. Mouse PEG3 is located on the proximal region of chromosome 7 which is syntenic to the long arm of human chromosome 19. It has been reported that a loss of heterozygosity (LOH) of chromosome 19q occurs frequently in several glioma types. Results We isolated human PEG3 cDNA. Both human and mouse PEG3 were strongly expressed in the adult brain and the PEG3 protein was localized in the nuclei of both neurones and glial cells. A significant decrease in PEG3 expression was more commonly observed in glioma cell lines as compared with that in primary cultures of astrocytes. Transfection of PEG3 cDNA in a glioma cell line resulted in a loss of tumorigenicity in nude mice. Conclusions The human PEG3 gene is a paternally expressed imprinted gene. Introduction of PEG3 cDNA into the glioma cells suggests that human PEG3 protein functions as a tumour suppressor. Human PEG3 is located on 19q13.4 and is one of the candidates for tumour suppressor genes that are predicted to be sited in gliomas.
-
mouse peg9 dlk1 and human peg9 dlk1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes mouse meg3 gtl2 and human meg3
Genes to Cells, 2000Co-Authors: Shin Kobayashi, Naoki Miyoshi, Kohzo Aisaka, Hirotaka Wagatsuma, Masaaki Yamazaki, Hiroyuki Tashiro, Hitoshi Ichikawa, Atsuo Ogura, Takashi Kohda, Misao OhkiAbstract:BACKGROUND: Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes. RESULTS: A novel paternally expressed mouse imprinted gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two genes form imprinted gene clusters with the reciprocally imprinted mouse Meg3/Gtl2 and human MEG3 genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. CONCLUSIONS: As DNA chip technology allows us to quickly screen a large number of genes, using this technology to search for imprinted genes could accelerate the identification of genes responsible for human and mouse genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.
-
mouse peg9 dlk1 and human peg9 dlk1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes mouse meg3 gtl2 and human meg3
Genes to Cells, 2000Co-Authors: Shin Kobayashi, Naoki Miyoshi, Kohzo Aisaka, Hirotaka Wagatsuma, Masaaki Yamazaki, Hiroyuki Tashiro, Hitoshi Ichikawa, Takashi Kohda, Ryuichi Ono, Atsuo OguraAbstract:Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes. A novel paternally expressed mouse imprinted gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two genes form imprinted gene clusters with the reciprocally imprinted mouse Meg3/Gtl2 and human MEG3 genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. As DNA chip technology allows us to quickly screen a large number of genes, using this technology to search for imprinted genes could accelerate the identification of genes responsible for human and mouse genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.
-
PEG3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein
Nature Genetics, 1996Co-Authors: Yoshimi Kuroiwa, Rika Suzuki, Minesuke Yokoyama, Tomoko Kanekoishino, M Tada, L. L. Li, Fusako Kagitani, Takashi Kohda, Toshihiko ShiroishiAbstract:Genetic and embryological studies in the mouse demonstrated functional differences between parental chromosomes during development1–3. This is due to imprinted genes whose expression is dependent on their parental origin4,5. In a recent systematic screen for imprinted genes, we detected PEG3 (paternally expressed gene 3)6. PEG3 is not expressed in parthenogenones. In interspecific hybrids, only the paternal copy of the gene is expressed in the embryos, individual tissues examined in d9.5–13.5 embryos, neonates and adults. PEG3 mRNA is a 9 kb transcript encoding an unusual zinc finger protein with eleven widely spaced C2H2 type motifs and two groups of amino acid repeats. PEG3 is expressed in early somites, branchial arches and other mesodermal tissues, as well as in the hypothalamus. PEG3 maps to the proximal region of chromosome 7. Consistent with our findings, maternal duplication of the proximal chromosome 7 causes neonatal lethality7–9. This region is syntenic with human chromosome 19q13.1–13.3 (refs 10,11), where the genes for myotonic dystrophy and a putative tumour suppressor gene are located12,13.
-
peg1 mest imprinted gene on chromosome 6 identified by cdna subtraction hybridization
Nature Genetics, 1995Co-Authors: Tomoko Kanekoishino, Naoki Miyoshi, Stephane Viville, Minesuke Yokoyama, Yoshimi Kuroiwa, Fumitoshi Ishino, Sheila C. Barton, R. Suzuki, Takashi Kohda, M. Azim SuraniAbstract:Parthenogenesis in the mouse is embryonic lethal partly because of imprinted genes that are expressed only from the paternal genome. In a systematic screen using subtraction hybridization between cDNAs from normal and parthenogenetic embryos, we initially identified two apparently novel imprinted genes, Peg1 and PEG3. Peg1 (paternally expressed gene 1) or Mest, the first imprinted gene found on the mouse chromosome 6, may contribute to the lethality of parthenogenones and of embryos with a maternal duplication for the proximal chromosome 6. Peg1/Mest is widely expressed in mesodermal tissues and belongs to the alpha/beta hydrolase fold family. A similar approach with androgenones can be used to identify imprinted genes that are expressed from the maternal genome only.
Shin Kobayashi - One of the best experts on this subject based on the ideXlab platform.
-
tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line
Genes to Cells, 2001Co-Authors: Takashi Kohda, Shin Kobayashi, Kohzo Aisaka, Yoshimi Kuroiwa, Akio Asai, Goro Nagashima, Michihiro C Yoshida, Yasumitsu Kondo, Naoto KagiyamaAbstract:Background Mouse imprinted gene PEG3 encodes a large C2H2 type zinc finger protein with unique characteristics. PEG3 knockout mice were found to show an impairment in maternal behaviour of the adult female. Mouse PEG3 is located on the proximal region of chromosome 7 which is syntenic to the long arm of human chromosome 19. It has been reported that a loss of heterozygosity (LOH) of chromosome 19q occurs frequently in several glioma types. Results We isolated human PEG3 cDNA. Both human and mouse PEG3 were strongly expressed in the adult brain and the PEG3 protein was localized in the nuclei of both neurones and glial cells. A significant decrease in PEG3 expression was more commonly observed in glioma cell lines as compared with that in primary cultures of astrocytes. Transfection of PEG3 cDNA in a glioma cell line resulted in a loss of tumorigenicity in nude mice. Conclusions The human PEG3 gene is a paternally expressed imprinted gene. Introduction of PEG3 cDNA into the glioma cells suggests that human PEG3 protein functions as a tumour suppressor. Human PEG3 is located on 19q13.4 and is one of the candidates for tumour suppressor genes that are predicted to be sited in gliomas.
-
mouse peg9 dlk1 and human peg9 dlk1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes mouse meg3 gtl2 and human meg3
Genes to Cells, 2000Co-Authors: Shin Kobayashi, Naoki Miyoshi, Kohzo Aisaka, Hirotaka Wagatsuma, Masaaki Yamazaki, Hiroyuki Tashiro, Hitoshi Ichikawa, Atsuo Ogura, Takashi Kohda, Misao OhkiAbstract:BACKGROUND: Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes. RESULTS: A novel paternally expressed mouse imprinted gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two genes form imprinted gene clusters with the reciprocally imprinted mouse Meg3/Gtl2 and human MEG3 genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. CONCLUSIONS: As DNA chip technology allows us to quickly screen a large number of genes, using this technology to search for imprinted genes could accelerate the identification of genes responsible for human and mouse genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.
-
mouse peg9 dlk1 and human peg9 dlk1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes mouse meg3 gtl2 and human meg3
Genes to Cells, 2000Co-Authors: Shin Kobayashi, Naoki Miyoshi, Kohzo Aisaka, Hirotaka Wagatsuma, Masaaki Yamazaki, Hiroyuki Tashiro, Hitoshi Ichikawa, Takashi Kohda, Ryuichi Ono, Atsuo OguraAbstract:Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes. A novel paternally expressed mouse imprinted gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two genes form imprinted gene clusters with the reciprocally imprinted mouse Meg3/Gtl2 and human MEG3 genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. As DNA chip technology allows us to quickly screen a large number of genes, using this technology to search for imprinted genes could accelerate the identification of genes responsible for human and mouse genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.
Rosa Maria Correra - One of the best experts on this subject based on the ideXlab platform.
-
the imprinted gene pw1 PEG3 regulates skeletal muscle growth satellite cell metabolic state and self renewal
Scientific Reports, 2018Co-Authors: Rosa Maria Correra, David Ollitrault, Mariana Valente, Alessia Mazzola, Bjorn T Adalsteinsson, Anne C FergusonsmithAbstract:Pw1/PEG3 is an imprinted gene expressed from the paternally inherited allele. Several imprinted genes, including Pw1/PEG3, have been shown to regulate overall body size and play a role in adult stem cells. Pw1/PEG3 is expressed in muscle stem cells (satellite cells) as well as a progenitor subset of muscle interstitial cells (PICs) in adult skeletal muscle. We therefore examined the impact of loss-of-function of Pw1/PEG3 during skeletal muscle growth and in muscle stem cell behavior. We found that constitutive loss of Pw1/PEG3 function leads to a reduced muscle mass and myofiber number. In newborn mice, the reduction in fiber number is increased in homozygous mutants as compared to the deletion of only the paternal Pw1/PEG3 allele, indicating that the maternal allele is developmentally functional. Constitutive and a satellite cell-specific deletion of Pw1/PEG3, revealed impaired muscle regeneration and a reduced capacity of satellite cells for self-renewal. RNA sequencing analyses revealed a deregulation of genes that control mitochondrial function. Consistent with these observations, Pw1/PEG3 mutant satellite cells displayed increased mitochondrial activity coupled with accelerated proliferation and differentiation. Our data show that Pw1/PEG3 regulates muscle fiber number determination during fetal development in a gene-dosage manner and regulates satellite cell metabolism in the adult.
-
pw1 PEG3 regulates skeletal muscle growth and satellite cell self renewal
2016Co-Authors: Rosa Maria CorreraAbstract:Pw1/PEG3 is a parentally imprinted gene expressed from the paternal allele. It is expressed in all adult progenitor/stem cell populations examined to date including muscle satellite cells. We examined the impact of loss-of-function of Pw1/PEG3 in skeletal muscle, a tissue that greatly contributes to body mass. We found that constitutive loss of Pw1/PEG3 results in reduced muscle mass resulting from a decrease in muscle fiber number. The reduced fiber number is present at birth. Mice lacking both the paternal and maternal alleles display a lower fiber number as compared to mice carrying the paternal deletion, suggesting that the maternal allele is functional during prenatal development. Hybrid analyses (C57BL6J and Cast/Ei) of muscle tissue reveal a bi-allelic expression of Pw1/PEG3 around 10%. Pw1/PEG3 is strongly up-regulated in response to muscle injury. Using the constitutive Pw1/PEG3 knock out mouse, we observed that satellite cells display a reduced self-renewal capacity following muscle injury. Pw1/PEG3 is expressed in satellite cells as well as a subset of muscle interstitial cells (PICs). To determine the specific role of Pw1/PEG3 in satellite cells, we crossed our conditional Pw1/PEG3 allele with the Pax7-CreER line. Interestingly, these mice displayed a more pronounced phenotype of impaired regeneration revealing a clear and direct role for Pw1/PEG3 in satellite cells. Taken together, our data show that Pw1/PEG3 plays a role during fetal development in the determination of muscle fiber number that is gene-dosage dependent and plays a specific role in muscle satellite cell self-renewal.
-
a novel mutant allele of pw1 PEG3 does not affect maternal behavior or nursing behavior
PLOS Genetics, 2016Co-Authors: Annelyse Denizot, Giovanna Marazzi, Rosa Maria Correra, Alessia Mazzola, Vanessa Besson, Izolina Lopes, Jeanremy Courbard, David SassoonAbstract:Parental imprinting is a mammalian-specific form of epigenetic regulation in which one allele of a gene is silenced depending on its parental origin. Parentally imprinted genes have been shown to play a role in growth, metabolism, cancer, and behavior. Although the molecular mechanisms underlying parental imprinting have been largely elucidated, the selective advantage of silencing one allele remains unclear. The mutant phenotype of the imprinted gene, Pw1/PEG3, provides a key example to illustrate the hypothesis on a coadaptation between mother and offspring, in which Pw1/PEG3 is required for a set of essential maternal behaviors, such as nursing, nest building, and postnatal care. We have generated a novel Pw1/PEG3 mutant allele that targets the last exon for the PW1 protein that contains >90% of the coding sequence resulting in a loss of Pw1/PEG3 expression. In contrast to previous reports that have targeted upstream exons, we observe that maternal behavior and lactation are not disrupted upon loss of Pw1/PEG3. Both paternal and homozygous Pw1/PEG3 mutant females nurse and feed their pups properly and no differences are detected in either oxytocin neuron number or oxytocin plasma levels. In addition, suckling capacities are normal in mutant pups. Consistent with previous reports, we observe a reduction of postnatal growth. These results support a general role for Pw1/PEG3 in the regulation of body growth but not maternal care and lactation.