Inheritance of an epigenetic change in the mouse: a new role for RNA

2007 ◽  
Vol 35 (3) ◽  
pp. 623-625 ◽  
Author(s):  
M. Rassoulzadegan ◽  
V. Grandjean ◽  
P. Gounon ◽  
F. Cuzin
Keyword(s):  
Epigenetic Modification ◽  
Epigenetic Variation ◽  
Epigenetic Change ◽  
Wild Type ◽  
Familial Disease ◽  
Phenotype Characteristic ◽  
Mendelian Analysis

Hereditary epigenetic variation, initially recognized and studied extensively in plants, had not been reported in mammals until recently. We have now identified the Kit locus as the first example of a paramutable gene of the mouse. Kit+/+ homozygotes born from Kittm1Alf/+ heterozygotes maintain and transmit to their progeny the white-spotted phenotype characteristic of the mutant heterozygote. Our observation of unusual amounts of RNA in the sperm of the paramutated (Kit*) males had led us to consider the possibility of RNA-mediated inheritance. A role for RNA was supported further by the efficient establishment of the epigenetic modification following microinjection in one-cell embryos of either sperm RNA of the paramutated males or of the Kit-specific microRNAs miR-221 and -222. In this article, we describe the phenotypes associated with the wild-type genome in the Kit* paramutated animals. Paramutation may be considered to be one possibility of epigenetic modification in the case of familial disease predispositions that are not fully accounted for by Mendelian analysis.

scholarly journals An epigenetic change in a moth is generated by temperature and transmitted to many subsequent generations mediated by RNA

2017 ◽  
Author(s):  
Jaroslav Pavelka ◽  
Simona Poláková ◽  
Věra Pavelková
Keyword(s):  
Small Rna ◽  
Future Generations ◽  
Evolutionary Significance ◽  
Epigenetic Change ◽  
Wild Type ◽  
Male And Female ◽  
Epigenetic Effect ◽  
Epigenetic Phenomenon ◽  
Practical Implications

AbstractBased on the presented results, the epigenetic phenomenon (paramutation) found in the short antennae (sa) mutation of the flour moth (Ephestia kuehniella) is probably determined by a small RNA (maybe piRNA) and transmitted in this way to subsequent generations through the male and female gametes. It is triggered by a change in the ambient environment; it persists for many generations (20 so far); during the epigenetic effect the original wild type appeared again. The epigenetic effect of the flour moth is induced by changes in ontogenetic development, such as increased temperature on pupae development, little nutritious food, different salts in food of certain chemicals into eggs. We found this mechanism may explain the intermittent clearance of this effect at some individuals and/or progeny of a pair in the generation chain in which the effect transfers. As the nature of the observed phenomenon could related to sirtuin genes, we hypothesize an association of these genes and non-coding small Piwi-interacting RNAs (piRNAs). The key is that the survival of RNA over many generations carries a number of practical implications. It is evident that the reaction to environmental change can manifest through RNA. It follows that there may be evolutionary significance in the long-term transmission of traits to future generations.

A genetic study on Gracilaria sjoestedtii

1988 ◽  
Vol 66 (10) ◽  
pp. 2022-2026 ◽  
Author(s):  
Xuecheng Zhang ◽  
John P. van der Meer
Keyword(s):  
Chromosome Number ◽  
Genetic Study ◽  
Maternal Inheritance ◽  
Intragenic Recombination ◽  
Wild Type ◽  
Multiple Alleles ◽  
Wild Type Clone ◽  
Nuclear Mutations ◽  
Diploid Gametes ◽  
Mendelian Analysis

In the present study on Gracilaria sjoestedtii, 41 mutants (40 pigmentation and 1 morphological) were isolated. These were characterized in a Mendelian analysis, which showed that 26 of the pigmentation variants are recessive nuclear mutations. The remaining 14 are cytoplasmic mutants having maternal inheritance and no detectable transmission through spermatia. A partial complementation analysis identified seven cistrons among the nuclear pigmentation mutants. Multiple alleles were encountered at five loci and apparent intragenic recombination was observed. No linkage between cistrons was found in recombination tests conducted thus far. Mitotic recombination leading to diploid gametes on tetrasporophytes was observed and used to construct triploid tetrasporophytes. The chromosome number of a wild-type clone of G. sjoestedtii was determined at meiosis as n = 29–30. Trivalent chromosomes were observed during meiosis in tetrasporophytes obtained by crossing female plants with tetrasporophytes. In culture tanks with flowing seawater, female gametophytes grew faster and appeared more suitable for vegetative propagation than male gametophytes and tetrasporophytes.

scholarly journals MMP12 Deletion Preferentially Attenuates Axial Stiffening of Aging Arteries

2019 ◽  
Vol 141 (8) ◽  
Author(s):  
Sonja A. Brankovic ◽  
Elizabeth A. Hawthorne ◽  
Xunjie Yu ◽  
Yanhang Zhang ◽  
Richard K. Assoian
Keyword(s):  
Wall Thickness ◽  
Axial Direction ◽  
Wild Type ◽  
Arterial Stiffening ◽  
Inner Radius ◽  
Age Dependent ◽  
Phenotype Characteristic ◽  
Arterial Biomechanics ◽  
Age And Sex

Arterial stiffening is a hallmark of aging, but how aging affects the arterial response to pressure is still not completely understood, especially with regard to specific matrix metalloproteinases (MMPs). Here, we performed biaxial inflation–extension tests on C57BL/6 mice to study the effects of age and MMP12, a major arterial elastase, on arterial biomechanics. Aging from 2 to 24 months leads to both circumferential and axial stiffening with stretch, and these changes are associated with an increased wall thickness, a decreased inner radius–wall thickness ratio, and a decreased in vivo axial stretch. Analysis of in vivo stretch and stress–stretch curves with arteries from age- and sex-matched wild-type (WT) and MMP12-null arteries demonstrates that MMP12 deletion attenuates age-dependent arterial stiffening, mostly in the axial direction. MMP12 deletion also prevents the aging-associated decrease in the in vivo stretch and, in general, leads to an axial mechanics phenotype characteristic of much younger mice. Circumferential arterial mechanics were much less affected by deletion of MMP12. We conclude that the induction of MMP12 during aging preferentially promotes axial arterial stiffening.

scholarly journals Genetic and Global Epigenetic Modification, Which Determines the Phenotype of Transgenic Rice?

2020 ◽  
Vol 21 (5) ◽  
pp. 1819
Author(s):  
Xiaoru Fan ◽  
Jingguang Chen ◽  
Yufeng Wu ◽  
CheeHow Teo ◽  
Guohua Xu ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Transgenic Plants ◽  
Plant Height ◽  
Epigenetic Modification ◽  
Epigenetic Changes ◽  
Wild Type ◽  
Global Methylation ◽  
Phenotypic Changes ◽  
Wide Range ◽  
Transgenic Lines

Transgenic technologies have been applied to a wide range of biological research. However, information on the potential epigenetic effects of transgenic technology is still lacking. Here, we show that the transgenic process can simultaneously induce both genetic and epigenetic changes in rice. We analyzed genetic, epigenetic, and phenotypic changes in plants subjected to tissue culture regeneration, using transgenic lines expressing the same coding sequence from two different promoters in transgenic lines of two rice cultivars: Wuyunjing7 (WYJ7) and Nipponbare (NP). We determined the expression of OsNAR2.1 in two overexpression lines generated from the two cultivars, and in the RNA interference (RNAi) OsNAR2.1 line in NP. DNA methylation analyses were performed on wild-type cultivars (WYJ7 and NP), regenerated lines (CK, T0 plants), segregation-derived wild-type from pOsNAR2.1-OsNAR2.1 (SDWT), pOsNAR2.1-OsNAR2.1, pUbi-OsNAR2.1, and RNAi lines. Interestingly, we observed global methylation decreased in the T0 regenerated line of WYJ7 (CK-WJY7) and pOsNAR2.1-OsNAR2.1 lines but increased in pUbi-OsNAR2.1 and RNAi lines of NP. Furthermore, the methylation pattern in SDWT returned to the WYJ7 level after four generations. Phenotypic changes were detected in all the generated lines except for SDWT. Global methylation was found to decrease by 13% in pOsNAR2.1-OsNAR2.1 with an increase in plant height of 4.69% compared with WYJ7, and increased by 18% in pUbi-OsNAR2.1 with an increase of 17.36% in plant height compared with NP. This suggests an absence of a necessary link between global methylation and the phenotype of transgenic plants with OsNAR2.1 gene over-expression. However, epigenetic changes can influence phenotype during tissue culture, as seen in the massive methylation in CK-WYJ7, T0 regenerated lines, resulting in decreased plant height compared with the wild-type, in the absence of a transformed gene. We conclude that in the transgenic lines the phenotype is mainly determined by the nature and function of the transgene after four generations of transformation, while the global epigenetic modification is dependent on the genetic background. Our research suggests an innovative insight in explaining the reason behind the occurrence of transgenic plants with random and undesirable phenotypes.

scholarly journals Somatic DNA demethylation generates tissue-specific methylation states and impacts flowering time

2021 ◽  
Author(s):  
Ben P Williams ◽  
Linsdey A Bechen ◽  
Deborah A Pohlmann ◽  
Mary Gehring
Keyword(s):  
Cytosine Methylation ◽  
Epigenetic Modification ◽  
Dna Demethylation ◽  
Dna Glycosylases ◽  
Wild Type ◽  
Gene Body Methylation ◽  
Tissue Specific ◽  
Coding Regions ◽  
Active Dna Demethylation ◽  
Somatic Tissues

Cytosine methylation is a reversible epigenetic modification to DNA. In plants, removal of cytosine methylation is accomplished by the four members of the DME family of 5-methylcytosine DNA glycosylases. Demethylation by DME is critical for seed development. Consequently, determining the function of the entire gene family in somatic tissues by mutant analysis has not been possible. Here, we bypassed the reproductive defects of dme mutants to create somatic quadruple homozygous mutants of the entire DME family. dme; ros1; dml2; dml3 (drdd) leaves exhibit hypermethylated genomes compared to both wild-type plants and rdd triple mutants, indicating functional redundancy among all four demethylases. Targets of demethylation include regions co-targeted by RNA-directed DNA methylation and, surprisingly, CG gene body methylation, indicating dynamic methylation at these little-understood sites. Additionally, many tissue-specific methylation differences are absent in drdd, suggesting a role for active demethylation in generating divergent epigenetic states across wild-type tissues. Furthermore, drdd plants display a striking early flowering phenotype, which is associated with 5′ hypermethylation and transcriptional down-regulation of FLOWERING LOCUS C. Active DNA demethylation is therefore required for proper methylation patterning across somatic tissues and defines the epigenetic landscape of both intergenic and coding regions.

The Epigenetic Modification of Epigallocatechin Gallate (EGCG) on Cancer

2020 ◽  
Vol 21 (11) ◽  
pp. 1099-1104
Author(s):  
Linqi Yang ◽  
Wenqi Zhang ◽  
Saiyam Chopra ◽  
Deeepjyot Kaur ◽  
Huibing Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Tumor Suppressor ◽  
Green Tea ◽  
Epigenetic Modification ◽  
Epigallocatechin Gallate ◽  
Signal Pathways ◽  
Epigenetic Change ◽  
Anti Cancer

: Among the major components of green tea, epigallocatechin-3-gallate (EGCG) is the most effective for its anti-cancer characteristics. The bulk of studies provide the mechanisms of suppressive function of EGCG are involved in alteration of cancer cell cycle, development, and apoptosis through activation/inhibition of several signal pathways. : Another mechanism that explains the multiple effects exerted by EGCG in cancer is the epigenetic change by DNA methylation or methyltransferases, histone acetylation or deacetylases, and no coding RNAs (micoRNAs). Furthermore, decontrolled expression of miRNA transcription has been tested to be directly regulated by oncogenic and tumor-suppressor transcription factors. Recently, several proteins have been identified as miRNA direct interactors by EGCG. However, the mechanisms explaining the action of miRNA being modulated by EGCG have not been completely understood yet. This review summarizes the state of epigenetic change being modulated by EGCG in a variety of cancers and oncogenic and tumor-suppressor transcription factors.

scholarly journals Strain-Dependent Influences on the Hypothalamo-Pituitary-Adrenal Axis Profoundly Affect the 7B2 and PC2 Null Phenotypes

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3438-3444 ◽  
Author(s):  
Juan R. Peinado ◽  
Virginie Laurent ◽  
Sang-Nam Lee ◽  
Bonnie W. Peng ◽  
John E. Pintar ◽  
...  
Keyword(s):  
Null Mouse ◽  
Wild Type ◽  
Acth Stimulation ◽  
Phenotypic Differences ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Phenotype Characteristic ◽  
Strain Dependent ◽  
Pituitary Adrenal Axis

Abstract Two null mouse models have previously been created to study the role of the prohormone convertase (PC2) and its helper protein 7B2; unexpectedly, the phenotypes of these two nulls differ profoundly, with the 7B2 but not the PC2 null dying at 5 wk. The genetic backgrounds of these two models differ, with the 7B2 null in a 129/SvEv (129) background and the PC2 null in a mixed C57BL/N6:129/SvEv (B6:129) background. Because background can contribute greatly to phenotype, we have here examined strain influence on the hypothalamo-pituitary-adrenal (HPA) axis and glucose levels in wild-type, 7B2 null, and PC2 null mice. Wild-type B6 and 129 mice differed in basal corticosterone and glucose levels. When 7B2 nulls were transferred onto the B6 background, they survived and showed greatly decreased circulating corticosterone and increased blood glucose levels, most likely due to the comparatively higher adrenal resistance of the B6 strain to ACTH stimulation. Circulating ACTH levels were increased over wild-type in the B6 7B2 null but did not reach levels as high as the 129 7B2 null. Conversely, when the mixed-strain PC2 nulls were bred into the 129 background at the N6 generation, they began to exhibit the Cushing’s-like phenotype characteristic of 129 7B2 null mice and died before 6 wk of age. Taken together, these results indicate that background effects are critical because they increase the phenotypic differences between the 7B2 and PC2 nulls and play a life-or-death role in the ACTH hypersecretion syndrome present in both 129 nulls.

scholarly journals Epigenetic silencing of recombinant AAV genomes by NP220 and the HUSH complex

2021 ◽  
Author(s):  
Anshuman Das ◽  
Madhuvanthi Vijayan ◽  
Eric M. Walton ◽  
V. Grace Stafford ◽  
David N. Fiflis ◽  
...  
Keyword(s):  
Potential Role ◽  
Human Gene ◽  
Epigenetic Modification ◽  
Epigenetic Silencing ◽  
Wild Type ◽  
Raav Vector ◽  
Double Stranded Dna ◽  
Factor Interactions ◽  
Episomal Dna

The single-stranded DNA genome of adeno-associated viruses (AAV) undergoes second-strand synthesis and transcription in the host cell nucleus. While wild-type AAV genomes are naturally silenced upon integration into the host genome, recombinant AAV (rAAV) genomes typically provide robust expression of transgenes persisting as extrachromosomal DNA or episomes. Episomal DNA associating with host histones are subject to epigenetic modifications, although the mechanisms underlying such are not well understood. Here, we provide evidence that the double-stranded DNA binding protein NP220, in association with the human silencing hub (HUSH) complex, mediates transcriptional silencing of single-stranded as well as self-complementary rAAV genomes. In cells lacking NP220 or other components of the HUSH complex, AAV genome transcript levels are increased and correlate with a marked reduction in repressive H3K9 histone methylation marks. We also provide evidence that the AAV capsid (serotype) can profoundly influence NP220-mediated mediated silencing of packaged genomes, indicating potential role(s) for capsid-genome or capsid-host factor interactions in regulating epigenetic silencing of rAAV genomes. Importance Recombinant AAV vectors can enable long term gene expression in a wide variety of tissues. However, transgene silencing has been reported in some human gene therapy clinical trials. Here, we demonstrate the human silencing hub (HUSH) complex can suppress transcript formation from rAAV vector genomes by epigenetic modification of associated host histones. Further, the AAV capsid appears to play an important role in this pathway. We postulate that modulation of epigenetic pathways could help improve rAAV expression.

scholarly journals An epigenetic breeding system in soybean for increased yield and stability

2017 ◽  
Author(s):  
Sunil Kumar Kenchanmane Raju ◽  
Mon-Ray Shao ◽  
Robersy Sanchez ◽  
Ying-Zhi Xu ◽  
Ajay Sandhu ◽  
...  
Keyword(s):  
Field Trials ◽  
Yield Stability ◽  
Specific Gene ◽  
Epigenetic Variation ◽  
Wild Type ◽  
Abiotic Stress Response ◽  
Abscisic Acid Biosynthesis ◽  
Plant Seed ◽  
Wide Range ◽  
Developmental Reprogramming

ABSTRACTEpigenetic variation has been associated with a wide range of adaptive phenotypes in plants, but there exist few direct means for exploiting this variation. RNAi suppression of the plant-specific gene,MutS HOMOLOG1(MSH1), in multiple plant species produces a range of developmental changes accompanied by modulation of defense, phytohormone, and abiotic stress response pathways. Thismsh1-conditioneddevelopmental reprogramming is retained independent of transgene segregation, giving rise to transgene-null ‘memory’ effects. An isogenic memory line crossed to wild type produces progeny families displaying increased variation in adaptive traits that respond to selection. This study investigates amenability of theMSH1system for inducing epigenetic variation in soybean that may be of value agronomically. We developed epi-line populations by crossing withmsh1-acquired soybean memory lines. Derived soybean epi-lines showed increase in variance for multiple yield-related traits including pods per plant, seed weight, and maturity time in both greenhouse and field trials. Selected epi-F2:4and epi-F2:5lines showed an increase in seed yield over wild type. By epi-F2:6, we observed a return of MSH1-derived enhanced growth back to wild type levels. Epi-populations also showed evidence of reduced epitype-by-environment (e × E) interaction, indicating higher yield stability. Transcript profiling of the soybean epi-lines identified putative signatures of enhanced growth behavior across generations. Genes related to cell cycle, abscisic acid biosynthesis, and auxin-response, particularly SMALL AUXIN UP RNAs (SAURs), were differentially expressed in epi-F2:4lines that showed increased yield when compared to epi-F2:6. These data support the potential ofmsh1-derived epigenetic variation in plant breeding for enhanced yield and yield stability.

scholarly journals Ecological divergence of DNA methylation patterns at distinct spatial scales

2019 ◽  
Author(s):  
H. De Kort ◽  
B. Panis ◽  
D. Deforce ◽  
F. Van Nieuwerburgh ◽  
O. Honnay
Keyword(s):  
Spatial Scale ◽  
Spatial Scales ◽  
Spatial Gradient ◽  
Epigenetic Variation ◽  
Biological Processes ◽  
Epigenetic Change ◽  
Trait Divergence ◽  
Scale Population ◽  
Genome Bisulfite Sequencing ◽  
Methylation Patterns

ABSTRACTAdaptive trait divergence between populations is regulated by genetic and non-genetic processes. Compared to genetic change, epigenetic change is unstable and short-lived, questioning its contribution to long-term adaptive potential. However, epigenetic change can accumulate over time, and may result in beneficial epigenetic memories where environments are heterogeneous. Diverging epigenetic memories have been observed across large spatial scales, and can persist through multiple generations even in the absence of the causative environmental stressor. It is unknown, however, how and to what extent epigenetic memories contribute to fine-scale population structure and evolution. Here, we performed whole genome bisulfite sequencing on 30 Fragaria vesca F1 plants originating from distinct ecological settings and grown in a controlled environment. Specifically, we compared methylation patterns between a steep, altitudinal gradient (<2 km) and a wide spatial gradient (>500 km). If epigenetic variation is random, arising from errors during replication and without evolutionary implications, one would expect similar amounts of epigenetic variation across populations and no spatial scale-effect. Here, we find that epigenetic memories arise even at fine spatial scale, and that both parallel and non-parallel biological processes underpin epigenetic divergence at distinct spatial scales. For example, demethylation of transposable elements consistently occurred at the large but not the small spatial scale, while methylation differentiation for most biological processes were shared between spatial scales. Acute drought stress did not result in significant epigenetic differentiation, indicating that repeated historical stress levels associated with heterogeneous environmental conditions are required for acquiring a stable epigenetic memory and for coping with future environmental change.

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