scholarly journals The chromatin modifiers SET-25 and SET-32 are required for initiation but not long-term maintenance of transgenerational epigenetic inheritance

2018 ◽  
Author(s):  
Rachel Woodhouse ◽  
Gabrielle Buchmann ◽  
Matthew Hoe ◽  
Dylan Harney ◽  
Mark Larance ◽  
...  
Keyword(s):  
Small Rna ◽  
Epigenetic Inheritance ◽  
Small Rna Sequencing ◽  
Chromatin Modifications ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
Secondary Sirnas ◽  
Rna Pathways ◽  
Term Maintenance

SummarySome epigenetic modifications are inherited from one generation to the next, providing a potential mechanism for the inheritance of environmentally acquired traits. Transgenerational inheritance of RNA interference phenotypes in Caenorhabditis elegans provides an excellent model to study this phenomenon, and whilst studies have implicated both chromatin modifications and small RNA pathways in heritable silencing their relative contributions remain unclear. Here we demonstrate that the histone methyltransferases SET-25 and SET-32 are required for the establishment of a transgenerational silencing signal but not for long-term maintenance of this signal between subsequent generations, suggesting that transgenerational epigenetic inheritance is a multi-step process with distinct genetic requirements for establishment and maintenance of heritable silencing. Furthermore, small RNA sequencing reveals that the abundance of secondary siRNAs (thought to be the effector molecules of heritable silencing) does not correlate with silencing phenotypes. Together, our results suggest that the current mechanistic models of epigenetic inheritance are incomplete.

scholarly journals Chromatin Modifiers SET-25 and SET-32 Are Required for Establishment but Not Long-Term Maintenance of Transgenerational Epigenetic Inheritance

Cell Reports ◽  
2018 ◽  
Vol 25 (8) ◽  
pp. 2259-2272.e5 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Gabriele Buchmann ◽  
Matthew Hoe ◽  
Dylan J. Harney ◽  
Jason K.K. Low ◽  
...  
Keyword(s):  
Epigenetic Inheritance ◽  
Transgenerational Epigenetic Inheritance ◽  
Term Maintenance ◽  
Chromatin Modifiers

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

scholarly journals RppH can faithfully replace TAP to allow cloning of 5’-triphosphate carrying small RNAs

2018 ◽  
Author(s):  
Miguel Vasconcelos Almeida ◽  
António Miguel de Jesus Domingues ◽  
Hanna Lukas ◽  
Maria Mendez-Lago ◽  
René F. Ketting
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Small Rna Sequencing ◽  
Cloning Efficiency ◽  
Library Preparation ◽  
Small Interfering Rnas ◽  
Rdrp Activity ◽  
C Elegans ◽  
Rna Pathways ◽  
Small Rna Species

AbstractRNA interference was first described in the nematode Caenorhabditis elegans. Ever since, several new endogenous small RNA pathways have been described and characterized to different degrees. Much like plants, but unlike Drosophila and mammals, worms have RNA-dependent RNA Polymerases (RdRPs) that directly synthesize small RNAs using other transcripts as a template. The very prominent secondary small interfering RNAs, also called 22G-RNAs, produced by the RdRPs RRF-1 and EGO-1 in C. elegans, maintain the 5’ triphosphate group, stemming from RdRP activity, also after loading into an Argonaute protein. This creates a technical issue, since 5’PPP groups decrease cloning efficiency for small RNA sequencing. To increase cloning efficiency of these small RNA species, a common practice in the field is the treatment of RNA samples, prior to library preparation, with Tobacco Acid pyrophosphatase (TAP). Recently, TAP production and supply was discontinued, so an alternative must be devised. We turned to RNA 5’ pyrophosphohydrolase (RppH), a commercially available pyrophosphatase isolated from E. coli. Here we directly compare TAP and RppH in their use for small RNA library preparation. We show that RppH-treated samples faithfully recapitulate TAP-treated samples. Specifically, there is enrichment for 22G-RNAs and mapped small RNA reads show no small RNA transcriptome-wide differences between RppH and TAP treatment. We propose that RppH can be used as a small RNA pyrophosphatase to enrich for triphosphorylated small RNA species and show that RppH- and TAP-derived datasets can be used in direct comparison.

scholarly journals Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic disorders

2020 ◽  
Author(s):  
Georges Raad ◽  
Fabrizio Serra ◽  
Luc Martin ◽  
Marie-Alix Derieppe ◽  
Jérôme Gilleron ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Epigenetic Inheritance ◽  
Metabolic Health ◽  
Western Diet ◽  
Chow Diet ◽  
Obesogenic Diet ◽  
Unbalanced Diet ◽  
Generation Male ◽  
Term Maintenance

AbstractObesity is a growing societal scourge responsible for approximately 4 million deaths worldwide. Recent studies have uncovered that paternal excessive weight induced by an unbalanced diet affects the metabolic health of offspring. These reports mainly employed single-generation male exposure. However, the consequences of multigenerational unbalanced diet feeding on the metabolic health of progeny remain largely unknown. Here, we show that maintaining paternal western diet feeding for five consecutive generations in mice induces a gradual enhancement in fat mass and related metabolic diseases over generations. Strikingly, chow-diet-fed progenies from these multigenerational western-diet-fed males develop a “healthy” overweight phenotype that is not reversed after 4 subsequent generations. Mechanistically, sperm RNA microinjection experiments into zygotes suggest that sperm RNAs are sufficient for establishment but not for long-term maintenance of epigenetic inheritance of metabolic pathologies. Progressive and permanent metabolic deregulation induced by successive paternal western-diet-fed generations may contribute to the worldwide epidemic of metabolic diseases.

scholarly journals Multigenerational Regulation of the Caenorhabditis elegans Chromatin Landscape by Germline Small RNAs

2019 ◽  
Vol 53 (1) ◽  
pp. 289-311 ◽  
Author(s):  
Natasha E. Weiser ◽  
John K. Kim
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Small Rnas ◽  
Model Organism ◽  
Epigenetic Inheritance ◽  
Small Interfering Rnas ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Small Noncoding Rnas ◽  
Rna Pathways

In animals, small noncoding RNAs that are expressed in the germline and transmitted to progeny control gene expression to promote fertility. Germline-expressed small RNAs, including endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), drive the repression of deleterious transcripts such as transposons, repetitive elements, and pseudogenes. Recent studies have highlighted an important role for small RNAs in transgenerational epigenetic inheritance via regulation of heritable chromatin marks; therefore, small RNAs are thought to convey an epigenetic memory of genomic self and nonself elements. Small RNA pathways are highly conserved in metazoans and have been best described for the model organism Caenorhabditis elegans. In this review, we describe the biogenesis, regulation, and function of C. elegans endo-siRNAs and piRNAs, along with recent insights into how these distinct pathways are integrated to collectively regulate germline gene expression, transgenerational epigenetic inheritance, and ultimately, animal fertility.

scholarly journals Small RNA Sequencing for Profiling MicroRNAs in Long-Term Preserved Formalin-Fixed and Paraffin-Embedded Non-Small Cell Lung Cancer Tumor Specimens

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121521 ◽  
Author(s):  
Daniel H. Buitrago ◽  
Santosh K. Patnaik ◽  
Kyuichi Kadota ◽  
Eric Kannisto ◽  
David R. Jones ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Rna Sequencing ◽  
Small Rna ◽  
Small Cell ◽  
Small Rna Sequencing ◽  
Small Cell Lung ◽  
Cancer Tumor ◽  
Formalin Fixed

Efficacious long-term maintenance therapy with pantoprazole (PAN) in patients with Zollinger-Ellison syndrome

2001 ◽  
Vol 120 (5) ◽  
pp. A613-A613
Author(s):  
P BORNMAN ◽  
K RADEBOLD ◽  
H DEBAERE ◽  
L VENTER ◽  
H HEINZE ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Zollinger Ellison Syndrome ◽  
Term Maintenance
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