Epigenetics
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Image:Molbio-Header.svg
This article is part of the series on:
Gene expression
a Molecular biology topic (portal)
(Glossary)
Introduction to Genetics
General flow: DNA > RNA > Protein
special transfers (RNA > RNA,
RNA > DNA, Protein > Protein)
Genetic code
Transcription
Transcription (Transcription factors,
RNA Polymerase,promoter)
post-transcriptional modification
(hnRNA,Splicing)
Translation
Translation (Ribosome,tRNA)
post-translational modification
(functional groups, peptides,
structural changes)
gene regulation
epigenetic regulation (Hox genes,
Genomic imprinting)
transcriptional regulation
post-transcriptional regulation
(sequestration,
alternative splicing,miRNA)
post-translational regulation
(reversible,irrevesible)
For the unfolding of an organism or the theory that plants and animals develop in this way, see Epigenesis (biology).
In biology, the term epigenetics refers to changes in gene expression. These changes may remain through cell divisions for the remainder of the cell's life. Sometimes the changes last for multiple generations. However, there is no change in the underlying DNA sequence of the organism,[1] instead, environmental factors cause the organism's genes to behave (or "express themselves") differently.[2] The best example of epigenetic changes in eukaryotic biology is the process of cellular differentiation. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo which in turn become fully differentiated cells. In other words, a single fertilized egg cell - the zygote - changes into the many cell types including neurons, muscle cells, epithelium, blood vessels et cetera as it continues to divide. It does so by a process of activating some genes while silencing others.[3]
Contents
[hide]
* 1 Etymology and definitions
* 2 Molecular basis of epigenetics
* 3 Mechanisms
o 3.1 DNA methylation and chromatin remodeling
o 3.2 RNA transcripts and their encoded proteins
o 3.3 Prions
o 3.4 Structural inheritance systems
* 4 Functions and consequences
o 4.1 Development
o 4.2 Medicine
o 4.3 Evolution
* 5 Epigenetic effects in humans
o 5.1 Genomic imprinting and related disorders
o 5.2 Transgenerational epigenetic observations
o 5.3 Cancer and developmental abnormalities
* 6 Epigenetics in microorganisms
* 7 See also
* 8 Further reading
* 9 Notes and references
* 10 External links
[edit] Etymology and definitions
The word epigenetics has had many definitions, and much of the confusion surrounding its usage relates to these definitions having changed over time. Initially it was used in a broader, less specific sense but it has become more narrowly linked to specific molecular phenomena occurring in organisms.[4]
Epigenetics (as in "epigenetic landscape") was coined by C. H. Waddington in 1942 as a portmanteau of the words genetics and epigenesis.[5] Epigenesis (see contrasting principle of preformationism) is an older word to describe the differentiation of cells from their initial totipotent state in embryonic development. When Waddington coined the term the physical nature of genes and their role in heredity was not known; he used it as a conceptual model of how genes might interact with their surroundings to produce a phenotype.
Robin Holliday defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms."[6] Thus epigenetic can be used to describe any aspect other than DNA sequence that influences the development of an organism.
The modern usage of the word is more narrow, referring to heritable traits (over rounds of cell division and sometimes transgenerationally) that do not involve changes to the underlying DNA sequence.[7] The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" genetics; thus epigenetic traits exist on top of or in addition to the traditional molecular basis for inheritance.
The similarity of the word to "genetics" has generated many parallel usages. The "epigenome" is a parallel to the word "genome," and refers to the overall epigenetic state of a cell. The phrase "genetic code" has also been adapted—the "epigenetic code" has been used to describe the set of epigenetic features that create different phenotypes in different cells. Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for; more typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the histone code or DNA methylation patterns.
Epigenetic was also used by the psychologist Erik Erikson in his Psychosocial development theory, however that usage is of primarily historical interest.[8]
[edit] Molecular basis of epigenetics
The molecular basis of epigenetics is complex. It involves modifications of the activation of certain genes, but not the basic structure of DNA. Additionally, the chromatin proteins associated with DNA may be activated or silenced. What this means is that every cell in your body has the same instruction manual, but different cell types are using different chapters. Your neurons, for example, contain the DNA instructions on how to make your fingernails- but in neurons, those genes are turned off. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the course of one individual organism's lifetime, but some epigenetic changes are inherited from one generation to the next.[9] Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.
Epigenetic research uses a wide range of molecular biologic techniques to further our understanding of epigenetic phenomena, including chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing. Furthermore, the use of bioinformatic methods is playing an increasing role (computational epigenetics).
[edit] Mechanisms
Several types of epigenetic inheritance systems may play a role in what has become known as cell memory:[10]
[edit] DNA methylation and chromatin remodeling
DNA associates with histone proteins to form chromatin.
DNA associates with histone proteins to form chromatin.
Because the phenotype of a cell or individual is affected by which of its genes are transcribed, heritable transcription states can give rise to epigenetic effects. There are several layers of regulation of gene expression. One way that genes are regulated is through the remodeling of chromatin. Chromatin is the complex of DNA and the histone proteins with which it associates. Histone proteins are little spheres that DNA wraps around. If the way that DNA is wrapped around the histones changes, gene expression can change as well. Chromatin remodeling is initiated by one of two things:
1. The first way is post translational modification of the amino acids that make up histone proteins. Histone proteins are made up of long chains of amino acids. If you change the amino acids that are in the chain, you can change the shape of the histone sphere. DNA is not completely unwound during replication. It is possible, then, that the modified histones may be carried into each new copy of the DNA. Once there, these histones may act as templates, initiating the surrounding new histones to be shaped in the new way. By altering the shape of the histones around it, these modified histones would ensure that a differe
* Oskar Hertwig, 1849-1922. Biological problem of today: preformation or epigenesis? The basis o
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Image:Molbio-Header.svg
This article is part of the series on:
Gene expression
a Molecular biology topic (portal)
(Glossary)
Introduction to Genetics
General flow: DNA > RNA > Protein
special transfers (RNA > RNA,
RNA > DNA, Protein > Protein)
Genetic code
Transcription
Transcription (Transcription factors,
RNA Polymerase,promoter)
post-transcriptional modification
(hnRNA,Splicing)
Translation
Translation (Ribosome,tRNA)
post-translational modification
(functional groups, peptides,
structural changes)
gene regulation
epigenetic regulation (Hox genes,
Genomic imprinting)
transcriptional regulation
post-transcriptional regulation
(sequestration,
alternative splicing,miRNA)
post-translational regulation
(reversible,irrevesible)
For the unfolding of an organism or the theory that plants and animals develop in this way, see Epigenesis (biology).
In biology, the term epigenetics refers to changes in gene expression. These changes may remain through cell divisions for the remainder of the cell's life. Sometimes the changes last for multiple generations. However, there is no change in the underlying DNA sequence of the organism,[1] instead, environmental factors cause the organism's genes to behave (or "express themselves") differently.[2] The best example of epigenetic changes in eukaryotic biology is the process of cellular differentiation. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo which in turn become fully differentiated cells. In other words, a single fertilized egg cell - the zygote - changes into the many cell types including neurons, muscle cells, epithelium, blood vessels et cetera as it continues to divide. It does so by a process of activating some genes while silencing others.[3]
Contents
[hide]
* 1 Etymology and definitions
* 2 Molecular basis of epigenetics
* 3 Mechanisms
o 3.1 DNA methylation and chromatin remodeling
o 3.2 RNA transcripts and their encoded proteins
o 3.3 Prions
o 3.4 Structural inheritance systems
* 4 Functions and consequences
o 4.1 Development
o 4.2 Medicine
o 4.3 Evolution
* 5 Epigenetic effects in humans
o 5.1 Genomic imprinting and related disorders
o 5.2 Transgenerational epigenetic observations
o 5.3 Cancer and developmental abnormalities
* 6 Epigenetics in microorganisms
* 7 See also
* 8 Further reading
* 9 Notes and references
* 10 External links
[edit] Etymology and definitions
The word epigenetics has had many definitions, and much of the confusion surrounding its usage relates to these definitions having changed over time. Initially it was used in a broader, less specific sense but it has become more narrowly linked to specific molecular phenomena occurring in organisms.[4]
Epigenetics (as in "epigenetic landscape") was coined by C. H. Waddington in 1942 as a portmanteau of the words genetics and epigenesis.[5] Epigenesis (see contrasting principle of preformationism) is an older word to describe the differentiation of cells from their initial totipotent state in embryonic development. When Waddington coined the term the physical nature of genes and their role in heredity was not known; he used it as a conceptual model of how genes might interact with their surroundings to produce a phenotype.
Robin Holliday defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms."[6] Thus epigenetic can be used to describe any aspect other than DNA sequence that influences the development of an organism.
The modern usage of the word is more narrow, referring to heritable traits (over rounds of cell division and sometimes transgenerationally) that do not involve changes to the underlying DNA sequence.[7] The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" genetics; thus epigenetic traits exist on top of or in addition to the traditional molecular basis for inheritance.
The similarity of the word to "genetics" has generated many parallel usages. The "epigenome" is a parallel to the word "genome," and refers to the overall epigenetic state of a cell. The phrase "genetic code" has also been adapted—the "epigenetic code" has been used to describe the set of epigenetic features that create different phenotypes in different cells. Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for; more typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the histone code or DNA methylation patterns.
Epigenetic was also used by the psychologist Erik Erikson in his Psychosocial development theory, however that usage is of primarily historical interest.[8]
[edit] Molecular basis of epigenetics
The molecular basis of epigenetics is complex. It involves modifications of the activation of certain genes, but not the basic structure of DNA. Additionally, the chromatin proteins associated with DNA may be activated or silenced. What this means is that every cell in your body has the same instruction manual, but different cell types are using different chapters. Your neurons, for example, contain the DNA instructions on how to make your fingernails- but in neurons, those genes are turned off. Epigenetic changes are preserved when cells divide. Most epigenetic changes only occur within the course of one individual organism's lifetime, but some epigenetic changes are inherited from one generation to the next.[9] Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.
Epigenetic research uses a wide range of molecular biologic techniques to further our understanding of epigenetic phenomena, including chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing. Furthermore, the use of bioinformatic methods is playing an increasing role (computational epigenetics).
[edit] Mechanisms
Several types of epigenetic inheritance systems may play a role in what has become known as cell memory:[10]
[edit] DNA methylation and chromatin remodeling
DNA associates with histone proteins to form chromatin.
DNA associates with histone proteins to form chromatin.
Because the phenotype of a cell or individual is affected by which of its genes are transcribed, heritable transcription states can give rise to epigenetic effects. There are several layers of regulation of gene expression. One way that genes are regulated is through the remodeling of chromatin. Chromatin is the complex of DNA and the histone proteins with which it associates. Histone proteins are little spheres that DNA wraps around. If the way that DNA is wrapped around the histones changes, gene expression can change as well. Chromatin remodeling is initiated by one of two things:
1. The first way is post translational modification of the amino acids that make up histone proteins. Histone proteins are made up of long chains of amino acids. If you change the amino acids that are in the chain, you can change the shape of the histone sphere. DNA is not completely unwound during replication. It is possible, then, that the modified histones may be carried into each new copy of the DNA. Once there, these histones may act as templates, initiating the surrounding new histones to be shaped in the new way. By altering the shape of the histones around it, these modified histones would ensure that a differe
* Oskar Hertwig, 1849-1922. Biological problem of today: preformation or epigenesis? The basis o
