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

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 Transgenerational Epigenetic Inheritance Is Revealed as a Multi-step Process by Studies of the SET-Domain Proteins SET-25 and SET-32

2019 ◽  
Vol 12 ◽  
pp. 251686571984421 ◽  
Author(s):  
Rachel M Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Epigenetic Inheritance ◽  
Set Domain ◽  
Genetic Inheritance ◽  
Step Process ◽  
Transgenerational Epigenetic Inheritance ◽  
Multiple Generations ◽  
Mendelian Genetic ◽  
Chromatin Modifiers

It is now clear that heredity is not determined purely by Mendelian genetic inheritance; sometimes, epigenetic signals can be passed from parent to progeny for multiple generations. This phenomenon is termed transgenerational epigenetic inheritance (TEI), and examples have now been observed in multiple organisms including plants, flies, mice, and nematodes. Here we discuss the recent findings that TEI is a multi-step process and that the putative chromatin modifiers SET-25 and SET-32 are important in the establishment but not maintenance of silencing.

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.

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.

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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