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Jun Hao Tanon 9 November 2012
Transcript of Epigenetic Inheritance
Evolution In Four Dimensions: Genetic, Epigenetic, Behavioural, and Symbolic Variation In The History of Life, The MIT Press. 2005 Epigenetic Inheritance Systems (EIS) Transgenerational
Epigenetic Inheritance Long-term Transmission Genomic Imprinting Implications RNA Mediated EIS Structural Inheritance Systems Chromatin-marking Systems Steady-state Systems “One is asked to imagine a number of marbles rolling down a hill towards a wall. The marbles will compete for the grooves on the slope, and come to rest at the lowest points. These points represent the eventual cell fates, that is, tissue types.” Epigenetic Inheritance Epigenetic Inheritance “Epigenetics is the study of the processes that underlie developmental plasticity and canalization and that bring about persistent developmental effects in both prokaryotes and eukarotes” – C. H. Waddington, 1957 It is a component of Epigenetics.
It occurs when:
- environmentally-induced and developmental-regulated variations
- variations due to developmental noise
are transmitted to subsequent generations of cells or organisms narrow perspective Steady-state and self-sustaining feedback loop systems allow cells to maintain homeostasis. Different cell lineages have different steady-states and different sets of complex self-sustaining feedback loops. All cellular structures are made up of three-dimensional proteins, for e.g. cell membranes, cytoskeletal structures, and cilia.
The production and folding of these structures requires self-templating, whereby the old structures were used as templates for the production of new structures. These structures are passed through self-templating from parent cells to daughter cells Chromatin-marking Systems is currently the most widely studied system. The chromatin structure is mainly made up of DNA, proteins and other macromolecules. Chromatin marks are binding proteins and chemical groups attached to the Histones or DNA that alter the activity of that particular gene region. RNAi also double up as a defence mechanism against dsRNA viruses. Studies also have shown RNAi are able to transmit information to adjacent and distant cells in plants. It is the accumulation of acquired epigenetic variation across several generations that result in the phenotypic expression and not due to changes in genes or environmental influences. Genes transmitted by parents are in different epigenetic states, if these differences persist during development and phenotypic effects, the genes are said to be “imprinted”
E.g. Prader-Willi Syndrome - caused by loss of paternally inherited genes and maternal imprinting
Angelman Syndrome - caused by loss of maternally inherited genes and paternal imprinting 1. Cancers involve cell-heritable epigenetic modifications
2. Hereditary diseases caused by epimutated imprinted genes
3. Prionic disease such Bovine spongiform encephalopathy, aka mad cow disease
4. Environmentally induced diseases, such as caused by starvation, have long-term effects (Lars Olov Bygren, 2001) Jablonka and Raz, 2009 “Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence” Wikipedia the inheritance of function and structural variation at cellular level other than the differences in genetic codes, which is passed on mitotically. This is also known cellular epigenetic inheritance. Steady-state Systems Structural Inheritance Systems Chromatin-marking Systems RNA Mediated EIS 1. Induction of gene transcription by external stimuli, by binding to the gene control region 2. With the right concentration of gene-product accumulated in the cell, the positive feedback loop becomes self-sustaining 3. When the cell divides the daughter inherit the gene’s active state, continuing the gene transcription 1. Existing cell continue to use its existing protein structure as template for folding newly produced protein 2. When the cell divides, the daughter cell inherit the old protein structures, and continue to use them as template for folding newly produced protein This system consists of RNA Interference (RNAi), and a recently described Long Non-coding RNA (lncRNA) taking part in DNA methylation.
When daughter cells inherit small RNA molecules from a parent cell, they activate the RNAi machinery and silence gene expression. The RNAi machinery works on two fronts, through siRNA (small interfering RNA) and miRNA (micro RNA). RNA Mediated EIS In a recently described Long Non-coding RNA (lncRNA)
taking part in DNA methylation.
These lncRNAs are mostly located on the opposite strand of a coding strand. Once these lncRNAs are transcribed, they become asscociated with methyltransferases.
These lncRNAs will then search for its complementing mRNA pair and deposit its methyltransferase, which will then add methyl groups to either on the DNA or to the histone tails, therefore silencing the gene. Epigenetic Inheritance includes the above plus:-
transgenerational epigenetic inheritance through meiotic cells (Jablonka & Raz 2009)
Heredity effects that by-pass the germline, such as:-
hormal and neural conditions (early developmental inputs)
symbionts and parasites (phenotypic transmission)
(Jablonka & Raz 2009) broad perspective It is the transmission of epigenetic variations between generations, and it is transmitted in two ways:- Genomic Imprinting Long-term Transmission Epidemiological research programs and medical practice can accommodate information like this, and develop ways recognizing, avoiding, and curing diseases caused by heritable epigenetic changes. Thank You Gill, Erkek and Peters, 2012 Wolf Reik, Wendy Dean, Jorn Walter, 2001 Arturas Petronis, 2010 Sir John Gurdon Shinya Yamanaka