scholarly journals The role of the paternal genome in the development of the mouse germ line

1997 ◽  
Vol 7 (11) ◽  
pp. 881-884 ◽  
Author(s):  
Maithreyi Narasimha ◽  
Sheila C. Barton ◽  
M.Azim Surani
Keyword(s):  
Germ Line ◽  
Paternal Genome

Evidence for a pathogenic role of BRCA1 L1705P and W1837X germ-line mutations

2016 ◽  
Vol 43 (5) ◽  
pp. 335-338 ◽  
Author(s):  
Anna P. Sokolenko ◽  
Nikita M. Volkov ◽  
Elena V. Preobrazhenskaya ◽  
Evgeny N. Suspitsin ◽  
Aigul R. Garifullina ◽  
...  
Keyword(s):  
Germ Line ◽  
Pathogenic Role ◽  
Germ Line Mutations

AMPK blocks chromatin activation and consequent R-loop formation to protect genome stability following acute starvation

2021 ◽  
Author(s):  
Bing Sun ◽  
McLean Sherrin ◽  
Richard Roy
Keyword(s):  
Dna Damage ◽  
Genome Stability ◽  
Germ Line ◽  
Critical Role ◽  
Significant Proportion ◽  
Loop Formation ◽  
C Elegans ◽  
Chromatin Activation ◽  
Acute Starvation

Abstract During periods of starvation organisms must modify both gene expression and metabolic pathways to adjust to the energy stress. We previously reported that C. elegans that lack AMPK have transgenerational reproductive defects that result from abnormally elevated H3K4me3 levels in the germ line following recovery from acute starvation1. Here we show that H3K4me3 is dramatically increased at promoters, driving aberrant transcription elongation that results in the accumulation of R-loops in the starved AMPK mutants. DRIP-seq analysis demonstrated that a significant proportion of the genome was affected by R-loop formation with a dramatic expansion in the number of R-loops at numerous loci, most pronounced at the promoter-TSS regions of genes in the starved AMPK mutants. The R-loops are transmissible into subsequent generations, likely contributing to the transgenerational reproductive defects typical of these mutants following starvation. Strikingly, AMPK null germ lines show considerably more RAD-51 foci at sites of R-loop formation, potentially sequestering it from its critical role at meiotic breaks and/or at sites of induced DNA damage. Our study reveals a previously unforeseen role of AMPK in maintaining genome stability following starvation, where in its absence R-loops accumulate, resulting in reproductive compromise and DNA damage hypersensitivity.

Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis

Development ◽  
2022 ◽  
Author(s):  
Yuki Naitou ◽  
Go Nagamatsu ◽  
Nobuhiko Hamazaki ◽  
Kenjiro Shirane ◽  
Masafumi Hayashi ◽  
...  
Keyword(s):  
Germ Cells ◽  
Splice Variant ◽  
Epithelial To Mesenchymal Transition ◽  
Functional Relationship ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Animal Kingdom ◽  
Mesenchymal Transition

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that Ovol2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) driving gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and consequently induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation.

Regulated expression of a murine class I gene in transgenic mice

1986 ◽  
Vol 6 (4) ◽  
pp. 1339-1342
Author(s):  
C Bieberich ◽  
G Scangos ◽  
K Tanaka ◽  
G Jay
Keyword(s):  
Transgenic Mice ◽  
Germ Line ◽  
Inbred Mice ◽  
Class I ◽  
Endogenous Gene ◽  
Histocompatibility Complex ◽  
Unique System ◽  
Regulated Expression ◽  
I Gene

The major histocompatibility complex class I genes play an essential role in the immune presentation of aberrant cells. To gain further insight into the regulation of the expression of these class I genes and to better define the functions of their protein products, we made use of the technique of gene transfer into the germ line of inbred mice. With the use of locus-specific DNA probes, we observed that a transgenic class I gene was expressed in a tissue-dependent fashion analogous to that of an endogenous class I gene. In addition, the level of expression of the transgenic gene was substantially higher that that of the endogenous gene. The availability of transgenic mice properly expressing a foreign murine class I gene provides a unique system to further define the role of the class I antigens in the maturation of the immune response and in determining the malignant and metastatic phenotypes of tumor cells.

scholarly journals Abnormal Micronuclear Telomeres Lead to an Unusual Cell Cycle Checkpoint and Defects in Tetrahymena Oral Morphogenesis

2008 ◽  
Vol 7 (10) ◽  
pp. 1712-1723 ◽  
Author(s):  
Karen E. Kirk ◽  
Christina Christ ◽  
Jennifer M. McGuire ◽  
Arun G. Paul ◽  
Mithaq Vahedi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mitotic Spindle ◽  
Tetrahymena Thermophila ◽  
Germ Line ◽  
Cell Cycle Checkpoint ◽  
Dna Damage Checkpoint ◽  
Telomeric Dna ◽  
Spindle Apparatus ◽  
Cycle Checkpoint

ABSTRACT Telomere mutants have been well studied with respect to telomerase and the role of telomere binding proteins, but they have not been used to explore how a downstream morphogenic event is related to the mutated telomeric DNA. We report that alterations at the telomeres can have profound consequences on organellar morphogenesis. Specifically, a telomerase RNA mutation termed ter1-43AA results in the loss of germ line micronuclear telomeres in the binucleate protozoan Tetrahymena thermophila. These cells also display a micronuclear mitotic arrest, characterized by an extreme delay in anaphase with an elongated, condensed chromatin and a mitotic spindle apparatus. This anaphase defect suggests telomere fusions and consequently a spindle rather than a DNA damage checkpoint. Most surprisingly, these mutants exhibit unique, dramatic defects in the formation of the cell's oral apparatus. We suggest that micronuclear telomere loss leads to a “dynamic pause” in the program of cortical development, which may reveal an unusual cell cycle checkpoint.

scholarly journals A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

2015 ◽  
Vol 36 (6) ◽  
pp. 886-899 ◽  
Author(s):  
Riyaz A. Mir ◽  
Aditya Bele ◽  
Sameer Mirza ◽  
Shashank Srivastava ◽  
Appolinaire A. Olou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Protein Interactions ◽  
Cell Cycle Progression ◽  
Germ Line ◽  
Regulatory Function ◽  
Cycle Progression ◽  
Cycle Arrest

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion ofEcdin cells causes cell cycle arrest, which is rescued by exogenousECD, demonstrating a requirement ofECDfor normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1in vitrofully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescueEcd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function.

DNA methyltransferase 1 (Dnmt1) mutation affects Snrpn imprinting in the mouse male germ line

Genome ◽  
2012 ◽  
Vol 55 (09) ◽  
pp. 673-682 ◽  
Author(s):  
Aabida Saferali ◽  
Sanny Moussette ◽  
Donovan Chan ◽  
Jacquetta Trasler ◽  
Taiping Chen ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Germ Line ◽  
Dna Methyltransferases ◽  
Dna Methyltransferase 1 ◽  
Loss Of Function ◽  
Male Germ Line ◽  
Epigenetic Remodeling ◽  
Genomic Imprints ◽  
Mature Spermatozoa

DNA methylation and DNA methyltransferases are essential for spermatogenesis. Mutations in the DNA methyltransferase Dnmt1 gene exert a paternal effect on epigenetic states and phenotypes of offspring, suggesting that DNMT1 is important for the epigenetic remodeling of the genome that takes place during spermatogenesis. However, the specific role of DNMT1 in spermatogenesis and the establishment of genomic imprints in the male germ line remains elusive. To further characterize the effect of DNMT1 deficiency on the resetting of methylation imprints during spermatogenesis, we analyzed the methylation profiles of imprinted regions in the spermatozoa of mice that were heterozygous for a Dnmt1 loss-of-function mutation. The mutation did not affect the H19 or IG differentially methylated regions (DMRs) that are usually highly methylated but led to a partial hypermethylation of the Snrpn DMR, a region that should normally be unmethylated in mature spermatozoa. This defect does not appear in mouse models with mutations in Dnmt3a and Mthfr genes and, therefore, it is specific for the Dnmt1 gene and is suggestive of a role of DNMT1 in imprint resetting or maintenance in the male germ line.

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