Transcript Alteration in DNA methylation and its transgenerational inheritance

Course Title:
Epigenetics
Lecture Titles:
Lecture I: General Overview and History of Epigenetics
Lecture II: DNA methylation
Lecture III: Alteration in DNA methylation and its transgenerational inheritance
Lecture IV: DNA methylation and genome stability
Lecture V: Epigenetic variation in genome evolution and crop improvement
Lecture VI: Histone modifications
Lecture VII: RNA interference
Lecture VIII: Epigenetics and gene expression
Lecture : TBD
Lecture : TBD
Lecture : Summary
Course Title:
Epigenetics
Lecture Titles:
Lecture I: General Overview and History of Epigenetics
Lecture II: DNA methylation
Lecture III: Alteration in DNA methylation and its transgenerational
inheritance
Lecture IV: DNA methylation and genome stability
Lecture V: Epigenetic variation in genome evolution and crop improvement
Lecture VI: Histone modifications
Lecture VII: Non-coding small RNA and RNA interference
Lecture VIII: Epigenetics and gene expression
Lecture : TBD
Lecture : TBD
Lecture : Summary
(toadflax, Leinkraut, Linaria vulgaris)
Cubas, P. et al. (1999) An epigenetic mutation responsible for natural variation in
floral symmetry. Nature 401, 157–161
DNA
methyltransferase
knockdown
worker
bee larvae
queen
Epigenetic Inheritance
mitotic stability/heritability
meiotic stability/
transgenerational inheritance
Persistence of epigenetic marks. Alterations that last less than one cell cycle
(green asterisk, a) do not qualify as epigenetic under the definition that strictly
requires heritability, whereas non-mutational changes that are transmitted from one
cell to its daughters (red asterisk, b) or between generations of an organism (blue
asterisk, c) do qualify.
Epigenetic modifications are widely accepted as playing a critical
role in the regulation of gene expression and thereby
contributing to the determination of the phenotype of multicellular
organisms. In general, these marks are cleared and reestablished each generation, but there have been reports in a
number of model organisms that at some loci in the genome
this clearing is incomplete. This phenomenon is referred to as
transgenerational epigenetic inheritance. Moreover, recent
evidence shows that the environment can stably influence the
establishment of the epigenome. Together, these findings
suggest that an environmental event in one generation could affect
the phenotype in subsequent generations, and these
somewhat Lamarckian ideas are stimulating interest from a broad
spectrum of biologists, from ecologists to health workers.
Heritable epigenetic polymorphisms, such as differential cytosine
methylation, can underlie phenotypic variation. Moreover, wild strains of
the plant Arabidopsis thaliana differ in many epialleles, and these can
influence the expression of nearby genes. However, to understand their
role in evolution, it is imperative to ascertain the emergence rate and
stability of epialleles, including those that are not due to structural
variation. We have compared genomewide DNA methylation among 10 A.
thaliana lines, derived 30 generations ago from a common ancestor.
Epimutations at individual positions were easily detected, and close to
30,000 cytosines in each strain were differentially methylated. In contrast,
larger regions of contiguous methylation were much more stable, and
the frequency of changes was in the same low range as that of DNA
mutations. Like individual positions, the same regions were often affected
by differential methylation in independent lines, with evidence for
recurrent cycles of forward and reverse mutations.
Transposable elements and short interfering RNAs have been causally
linked to DNA methylation. In agreement, differentially methylated sites
were farther from transposable elements and showed less association
with short interfering RNA expression than invariant positions. The
biased distribution and frequent reversion of epimutations have
important implications for the potential contribution of sequenceindependent epialleles to plant evolution.
Science September 23, 2011
Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants
Robert J. Schmitz,1,2 Matthew D. Schultz,1,2,3 Mathew G. Lewsey,1,2 Ronan C. O’Malley,2 Mark A. Urich,1,2
Ondrej Libiger,4
Nicholas J. Schork,4 Joseph R. Ecker1,2,5*
Epigenetic information, which may affect an organisms’ phenotype, can be stored and
stably inherited in the form of cytosine DNA methylation. Changes in DNA
methylation can produce meiotically stable epialleles that affect transcription and
morphology, but the rates of spontaneous gain or loss of DNA methylation are
unknown. We examined spontaneously occurring
variation in DNA methylation in Arabidopsis thaliana plants propagated by single-seed
descent for 30 generations. 114,287 CG single methylation
polymorphisms (SMPs) and 2485 CG differentially methylated regions (DMRs) were
identified, both of which show patterns of divergence compared to the ancestral state.
Thus, transgenerational epigenetic variation in DNA methylation may generate new
allelic states that alter transcription providing a mechanism for phenotypic diversity in
the absence of genetic mutation.
Science September 23, 2011
Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants
Robert J. Schmitz,1,2 Matthew D. Schultz,1,2,3 Mathew G. Lewsey,1,2 Ronan C. O’Malley,2 Mark A. Urich,1,2
Ondrej Libiger,4
Nicholas J. Schork,4 Joseph R. Ecker1,2,5*
“Regardless of their origin, the majority of epialleles
identified in this study are meiotically stable and
heritable across many generations in this population.
Understanding the basis for such transgenerational
instability and the mechanism(s) that trigger and/or
release these epiallelic states will be of great importance
for future studies.”
Science (2009)
Science (2010)
“Some authors use the term “variation” in
a technical sense, as implying a
modification directly due to the physical
conditions of life; and “variations” in this sense are
supposed not to be inherited; but who can say that
the dwarfed condition of shells in the brackish
waters of the Baltic, or dwarfed plants on Alpine
summits, or the thicker fur of an animal from far
northwards, would not in some cases be inherited
for at least a few generations (Darwin, 1859)?”
Thank you for your attention!