Mouse embryos with paternal duplication of an imprinted chromosome 7 region die at midgestation and lack placental spongiotrophoblast

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 265-270 ◽  
Author(s):  
K.J. McLaughlin ◽  
P. Szabo ◽  
H. Haegel ◽  
J.R. Mann
Keyword(s):  
Mouse Embryos ◽  
Chromosome 7 ◽  
Imprinted Genes ◽  
Uniparental Inheritance ◽  
Aberrant Expression ◽  
Distal Chromosome ◽  
Specific Activities ◽  
Androgenetic Embryos ◽  
Genomic Regions ◽  
Chromosome Regions

Imprinted genomic regions have been defined by the production of mice with uniparental inheritance or duplication of homologous chromosome regions. With most of the genome investigated, paternal duplication of only distal chromosomes 7 and 12 results in the lack of offspring, and prenatal lethality is presumed. Aberrant expression of imprinted genes in these two autosomal regions is therefore strongly implicated in the periimplantation lethality of androgenetic embryos. We report that mouse embryos with paternal duplication of distal chromosome 7 (PatDup.d7) die at midgestation and lack placental spongiotrophoblast. Thus, the much earlier death of androgenones must involve paternal duplication of other autosomal regions, acting independently of or synergistically with PatDup.d7. The phenotype observed is similar, if not identical to, that resulting from mutation of the imprinted distal chromosome 7 gene, Mash2, which in normal midgestation embryos exhibits spongiotrophoblast-specific maternally active/paternally inactive (m+/p-) allelic expression. Thus, the simplest explanation for the PatDup.d7 phenotype is p-/p- expression of this gene. We also confirm that PatDup.d7 embryos lack H19 RNA and posses excess Igf2 RNA as might be expected from the parental-specific activities of these genes in normal embryos.

Restriction Fragment Length Polymorphism and Divergence in the Genomic Regions of High and Low Recombination in Self-Fertilizing and Cross-Fertilizing Aegilops Species

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 423-434
Author(s):  
Jan Dvorřák ◽  
Ming-Cheng Luo ◽  
Zu-Li Yang
Keyword(s):  
Related Species ◽  
Gene Diversity ◽  
Single Copy ◽  
Species Variation ◽  
Recombination Rates ◽  
Distal Chromosome ◽  
Phylogenetic Status ◽  
Average Gene ◽  
Genomic Regions ◽  
Chromosome Regions

Abstract RFLP was investigated at 52 single-copy gene loci among six species of Aegilops, including both cross-fertilizing and self-fertilizing species. Average gene diversity (H) was found to correlate with the level of outcrossing. No relationship was found between H and the phylogenetic status of a species. In all six species, the level of RFLP at a locus was a function of the position of the locus on the chromosome and the recombination rate in the neighborhood of the locus. Loci in the proximal chromosome regions, which show greatly reduced recombination rates relative to the distal regions, were significantly less variable than loci in the distal chromosome regions in all six species. Variation in recombination rates was also reflected in the haplotype divergence between closely related species; loci in the chromosome regions with low recombination rates were found to be diverged less than those in the chromosome regions with high recombination rates. This relationship was not found among the more distantly related species.

scholarly journals Mechanism of imprinting on mouse distal chromosome 7

1998 ◽  
Vol 72 (3) ◽  
pp. 237-245 ◽  
Author(s):  
JUSTIN F-X. AINSCOUGH ◽  
ROSALIND M. JOHN ◽  
M. AZIM SURANI
Keyword(s):  
Chromosome 7 ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Critical Feature ◽  
Male Germline ◽  
Domain Type ◽  
Distal Chromosome ◽  
Type Mode ◽  
Single Allele ◽  
Female Germline

Genomic imprinting is an epigenetic mode of gene regulation that results in expression of the autosomal ‘imprinted’ genes from only a single allele, determined exclusively by parental origin. To date over 20 imprinted genes have been identified in mouse and man and these appear to lie in clusters in restricted regions on a subset of chromosomes. This may be a critical feature of imprinting suggesting a domain-type mode of regulation. Imprinted domains are replicated asynchronously, show sex-specific meiotic recombination frequencies and have CpG-rich regions that are differentially methylated, often associated with the imprinted genes themselves. Mouse distal chromosome 7 is one such domain, containing at least nine imprinted genes spanning over 1 Mb of DNA. For the maternally expressed p57Kip2 gene, passage through the female germline is essential to generate the active state, whereas passage through the male germline is needed to force the maternally expressed H19 gene into an inactive state. It is therefore possible that the mouse distal chromosome 7 imprinted domain is actually composed of two or more independently regulated subdomains.

scholarly journals Multiple Mechanisms Regulate Imprinting of the Mouse Distal Chromosome 7 Gene Cluster

1998 ◽  
Vol 18 (6) ◽  
pp. 3466-3474 ◽  
Author(s):  
Tamara Caspary ◽  
Michele A. Cleary ◽  
Catherine C. Baker ◽  
Xiao-Juan Guan ◽  
Shirley M. Tilghman
Keyword(s):  
Dna Methylation ◽  
Gene Cluster ◽  
Genomic Imprinting ◽  
Dna Methyltransferase ◽  
Regulatory Elements ◽  
Chromosome 7 ◽  
Imprinted Genes ◽  
Global Regulator ◽  
Loss Of Imprinting ◽  
Distal Chromosome

ABSTRACT Genomic imprinting is an epigenetic process that results in the preferential silencing of one of the two parental copies of a gene. Although the precise mechanisms by which genomic imprinting occurs are unknown, the tendency of imprinted genes to exist in chromosomal clusters suggests long-range regulation through shared regulatory elements. We characterize a 800-kb region on the distal end of mouse chromosome 7 that contains a cluster of four maternally expressed genes, H19, Mash2, Kvlqt1, andp57Kip2 , as well as two paternally expressed genes, Igf2 and Ins2, and assess the expression and imprinting of Mash2, Kvlqt1, andp57Kip2 during development in embryonic and extraembryonic tissues. Unlike Igf2 and Ins2, which depend on H19 for their imprinting,Mash2, p57Kip2 , andKvlqt1 are unaffected by a deletion of the H19gene region, suggesting that these more telomeric genes are not regulated by the mechanism that controls H19,Igf2, and Ins2. Mutations in humanp57Kip2 have been implicated in Beckwith-Wiedemann syndrome, a disease that has also been associated with loss of imprinting of IGF2. We find, however, that a deletion of the gene has no effect on imprinting within the cluster. Surprisingly, the three maternally expressed genes are regulated very differently by DNA methylation; p57Kip2 is activated, Kvlqt1 is silenced, and Mash2 is unaffected in mice lacking DNA methyltransferase. We conclude thatH19 is not a global regulator of imprinting on distal chromosome 7 and that the telomeric genes are imprinted by a separate mechanism(s).

scholarly journals G9a Histone Methyltransferase Contributes to Imprinting in the Mouse Placenta

2007 ◽  
Vol 28 (3) ◽  
pp. 1104-1113 ◽  
Author(s):  
Alexandre Wagschal ◽  
Heidi G. Sutherland ◽  
Kathryn Woodfine ◽  
Amandine Henckel ◽  
Karim Chebli ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Methylation ◽  
Histone Methyltransferase ◽  
Chromosome 7 ◽  
Gene Repression ◽  
Imprinted Genes ◽  
Set Domain ◽  
Imprinted Gene ◽  
Mouse Placenta ◽  
Distal Chromosome

ABSTRACT Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic expression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are marked by histone H3-K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET domain protein G9a. We found that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression was unchanged at the domains analyzed, in spite of a global loss of H3-K9 dimethylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is impaired in the absence of G9a, and this correlates with reduced levels of H3K9me2 and H3K9me3. These findings provide the first evidence for the involvement of an HMT and suggest that histone methylation contributes to imprinted gene repression in the trophoblast.

scholarly journals Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development

2007 ◽  
Vol 17 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Rocío M. Rivera ◽  
Paula Stein ◽  
Jamie R. Weaver ◽  
Jesse Mager ◽  
Richard M. Schultz ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Imprinted Genes ◽  
Aberrant Expression

scholarly journals ZFP57 dictates allelic expression switch of target imprinted genes

2021 ◽  
Vol 118 (5) ◽  
pp. e2005377118
Author(s):  
Weijun Jiang ◽  
Jiajia Shi ◽  
Jingjie Zhao ◽  
Qiu Wang ◽  
Dan Cong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mouse Embryos ◽  
The Other ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Imprinted Genes ◽  
Parent Of Origin

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin–dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.

scholarly journals The H19 Differentially Methylated Region Marks the Parental Origin of a Heterologous Locus without Gametic DNA Methylation

2004 ◽  
Vol 24 (9) ◽  
pp. 3588-3595 ◽  
Author(s):  
Kye-Yoon Park ◽  
Elizabeth A. Sellars ◽  
Alexander Grinberg ◽  
Sing-Ping Huang ◽  
Karl Pfeifer
Keyword(s):  
Dna Methylation ◽  
Mouse Chromosome ◽  
Germ Line ◽  
Transcriptional Silencing ◽  
Chromosome 7 ◽  
Differentially Methylated Region ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Chromosome 5 ◽  
The Third

ABSTRACT Igf2 and H19 are coordinately regulated imprinted genes physically linked on the distal end of mouse chromosome 7. Genetic analyses demonstrate that the differentially methylated region (DMR) upstream of the H19 gene is necessary for three distinct functions: transcriptional insulation of the maternal Igf2 allele, transcriptional silencing of paternal H19 allele, and marking of the parental origin of the two chromosomes. To test the sufficiency of the DMR for the third function, we inserted DMR at two heterologous positions in the genome, downstream of H19 and at the alpha-fetoprotein locus on chromosome 5. Our results demonstrate that the DMR alone is sufficient to act as a mark of parental origin. Moreover, this activity is not dependent on germ line differences in DMR methylation. Thus, the DMR can mark its parental origin by a mechanism independent of its own DNA methylation.

Lethality of a tritiated amino acid in early mouse embryos

Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 209-217
Author(s):  
Janet L. Wiebold ◽  
Gary B. Anderson
Keyword(s):  
Specific Activity ◽  
Subsequent Development ◽  
Blastocyst Stage ◽  
Mouse Embryos ◽  
Radiation Induced ◽  
Specific Activities ◽  
Tritiated Amino Acids ◽  
Early Mouse

2- to 4-cell and morula- to blastocyst-stage mouse embryos were cultured for 1 h in tritiated leucine at two specific activities and their subsequent development followed in vitro and in vivo (after transfer to recipients), respectively. 2- to 4-cell embryos that incorporated an average of 42 d.p.m. per embryo were impaired in their ability to develop to the morula and blastocyst stage. Recipients receiving morulae and blastocysts that had incorporated an average of 384 d.p.m. per embryo failed to produce young. Reduction of the specific activity improved the viability of embryos both in vitro and in vivo but development was still less than that of unlabelled embryos. Protein degradation curves were different for both 2- to 4-cell and morulato blastocyst-stage embryos labelled at the two different specific activities. Most studies using tritiated amino acids have employed higher specific activities than those used here and they may have to be reevaluated due to the possibility of radiation-induced artifacts.

scholarly journals Variation in Recombination Rate Is Shaped by Domestication and Environmental Conditions in Barley

2019 ◽  
Vol 36 (9) ◽  
pp. 2029-2039 ◽  
Author(s):  
Steven Dreissig ◽  
Martin Mascher ◽  
Stefan Heckmann
Keyword(s):  
Environmental Conditions ◽  
Recombination Rate ◽  
Wild Barley ◽  
Natural Populations ◽  
Recombination Rates ◽  
Distal Chromosome ◽  
Positive Linear Correlation ◽  
Short And Long Term ◽  
Underlying Mechanisms ◽  
Chromosome Regions

Abstract Meiotic recombination generates genetic diversity upon which selection can act. Recombination rates are highly variable between species, populations, individuals, sexes, chromosomes, and chromosomal regions. The underlying mechanisms are controlled at the genetic and epigenetic level and show plasticity toward the environment. Environmental plasticity may be divided into short- and long-term responses. We estimated recombination rates in natural populations of wild barley and domesticated landraces using a population genetics approach. We analyzed recombination landscapes in wild barley and domesticated landraces at high resolution. In wild barley, high recombination rates are found in more interstitial chromosome regions in contrast to distal chromosome regions in domesticated barley. Among subpopulations of wild barley, natural variation in effective recombination rate is correlated with temperature, isothermality, and solar radiation in a nonlinear manner. A positive linear correlation was found between effective recombination rate and annual precipitation. We discuss our findings with respect to how the environment might shape effective recombination rates in natural populations. Higher recombination rates in wild barley populations subjected to specific environmental conditions could be a means to maintain fitness in a strictly inbreeding species.

Localization of the Mouse Gene (Bc1) Encoding Neural BC1 RNA Near the Fibroblast Growth Factor 3 Locus (Fgf3) on Distal Chromosome 7

Genomics ◽  
1997 ◽  
Vol 44 (1) ◽  
pp. 153-154 ◽  
Author(s):  
Benjamin A. Taylor ◽  
Ann Navin ◽  
Boris V. Skryabin ◽  
Jürgen Brosius
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Mouse Gene ◽  
Chromosome 7 ◽  
Fibroblast Growth ◽  
Distal Chromosome
Sign in / Sign up

Export Citation Format

Share Document