Epigenetics

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Epigenetics is the study of changes to the [[Genome|genome]] and the heritability of said alterations. [[Gene expression|Gene expression]] within an [[Organism|organism]] can be altered by changes to the [[Genome|genome]], without the [[DNA|DNA]] sequence itself being changed, in response to its environment. This essentially results in a change in the [[Phenotype|phenotype]] without a change to the [[Genotype|genotype]].  
 
Epigenetics is the study of changes to the [[Genome|genome]] and the heritability of said alterations. [[Gene expression|Gene expression]] within an [[Organism|organism]] can be altered by changes to the [[Genome|genome]], without the [[DNA|DNA]] sequence itself being changed, in response to its environment. This essentially results in a change in the [[Phenotype|phenotype]] without a change to the [[Genotype|genotype]].  
  
This is mainly caused by the addition of specific chemical groups on to the genome, which can promote or inhibit the transcription of [[Genes|genes]] into [[Polypeptides|polypeptides]]. An example of epigenetic change is [[DNA methylation|DNA methylation]], which is the addition of a [[Methyl group|methyl group]] to [[Cytosine|cytosine]] by methyltransferases. This methylation prevents the binding of [[Transcription factor|transcription factors]] and therefore leads to a low rate of transcription of those genes. It is also due to positive feedback loops of gene regulatory proteins or to heritable modifications in chromatin<ref>Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts and Peter Walter. (2008) Molecular Biology of The Cell, Fifth Edition, New York: Garland Science.</ref>. The genome alterations are considered to be heritable, therefore the changes in gene expression of an organism may affect their offspring in subsequent generations<ref>Carey N. The epigenetics revolution. United Kingdom: Icon Books Ltd; 2012.</ref>. In other words, parents' past experience could be passed on to next generation which will make them have better characteristics than their parents.  
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This is mainly caused by the addition of specific chemical groups on to the genome, which can promote or inhibit the transcription of [[Genes|genes]] into [[Polypeptides|polypeptides]]. An example of epigenetic change is [[DNA methylation|DNA methylation]], which is the addition of a [[Methyl group|methyl group]] to [[Cytosine|cytosine]] by methyltransferases. The methyl group is added to the C5 atom of a cytosine base in a [[CpG Islands|CpG dinucleotide]] within the DNA. This methyl group originates from an S-adenosyl-L-methionine (SAM) molecule, and the process is catalysed by DNA methyltransferases (DNMTs)<ref>Herceg Z. Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors. Mutagenesis. 2007. 22(2), 91–103</ref>. This methylation prevents the binding of [[Transcription factor|transcription factors]] and therefore leads to a low rate of transcription of those genes. It is also due to positive feedback loops of gene regulatory proteins or to heritable modifications in chromatin<ref>Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts and Peter Walter. (2008) Molecular Biology of The Cell, Fifth Edition, New York: Garland Science.</ref>. The genome alterations are considered to be heritable, therefore the changes in gene expression of an organism may affect their offspring in subsequent generations<ref>Carey N. The epigenetics revolution. United Kingdom: Icon Books Ltd; 2012.</ref>. In other words, parents' past experience could be passed on to the&nbsp; next generation which will make them have better characteristics than their parents.  
  
The epigenome is a structure that consists of a histone octamer which tightly wrapped [[DNA|DNA]] is coiled, this fundimental repeating subunit is called the Nucleosome. Change to the epigenome results in conformational changes in the geometry of the genome. This “highlights” specific parts of the DNA sequence thus affecting transcription and, therefore, gene expression. Different cells have different active genes despite having similar DNA sequences. For example, [[Brain|brain]] cells and [[Liver|liver]] cells contain the same DNA sequence yet the expressed active genes are different. These histone modifications resulting in epigenetic change can be caused by over 150 chemical reactions such as [[Histone Acetylation|acetylation]], [[Methylation|methylation]] and [[Phosphorylation|phosphorylation]]<ref>Griffiths AJF, Wessler SR, Carroll SB, Doebley J. Introduction to genetic analysis, 11th ed. United States of America: W.H. Freeman and Company; 2015.</ref>.  
+
The epigenome is a structure that consists of a [[Histones|histone]] octamer which tightly wrapped [[DNA|DNA]] is coiled, this fundamental repeating subunit is called the [[Nucleosome|nucleosome]]. Changes to the epigenome results in conformational changes in the geometry of the genome. This “highlights” specific parts of the DNA sequence thus affecting [[Transcription|transcription]] and, therefore, gene expression. Different cells have different active genes despite having similar DNA sequences. For example, [[Brain|brain]] cells and [[Liver|liver]] cells contain the same DNA sequence yet the expressed active genes are different. These histone modifications resulting in epigenetic change can be caused by over 150 chemical reactions such as [[Histone Acetylation|acetylation]], [[Methylation|methylation]], [[Ubiquitination|ubiquitination]]&nbsp;and [[Phosphorylation|phosphorylation]]<ref>Griffiths AJF, Wessler SR, Carroll SB, Doebley J. Introduction to genetic analysis, 11th ed. United States of America: W.H. Freeman and Company; 2015.</ref>.  
  
Methylation is the addition of a methyl group onto a cytosine base, this results in the condensing of the dna-histone complex. meaning that theres a smaller area for transcriptional factors to bind to the genome.
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Methylation is the addition of a methyl group onto a cytosine base, this results in the condensing of the DNA-histone complex. Meaning that there's a smaller area for transcriptional factors to bind to the genome. [[Acetylation|Acetylation]] is the addition of an acetyl group to a [[DNA|DNA]] molecule, which enhances the molecules affinity for binding proteins to interact with specific sites in order to initiate [[Gene transcription|gene transcription]].  
  
 
Formerly, it was assumed that for proper cellular development and distinction to occur in mammals, the epigenome was fully erased through a 'reprogramming' process which happens twice; once during gamete formation and once during conception<ref>Alan Horsager(2014) Episona. Available at: https://www.episona.com/3-examples-transgenerational-epigenetic-inheritance/ (last accessed 18 Nov 2015)</ref>. It is reconstructed between generations. The methylation marks are supposed to be converted to hydroxymethylation which will be diluted as the cell divides<ref>University of Cambridge (25 Jan 2013) Available at: http://www.cam.ac.uk/research/news/scientists-discover-how-epigenetic-information-could-be-inherited (last accessed 18 Nov 2015)</ref>. Now, however, incomplete removal of epigenomes in specific genes have been found, suggesting that certain gene profiles are inherited epigenetically<ref name="[3]">Utahedu. 3. Utahedu. [Online]. Available from: http://learn.genetics.utah.edu/content/epigenetics/ [Accessed 20 November 2015].</ref>. Heritability of epigenetic modification has been observed in studies with mice. One such study revealed the transgenerational inheritance of the yellow coat colour phenotype in mice, resulting from the incomplete erasure of methylation marks when a silenced Avy allele is passed down through the female germline<ref>Morgan H, Sutherland H et al. Epigenetic inheritance at the agouti locus in the mouse. Nature Genetics 1999; 23(3)</ref>.  
 
Formerly, it was assumed that for proper cellular development and distinction to occur in mammals, the epigenome was fully erased through a 'reprogramming' process which happens twice; once during gamete formation and once during conception<ref>Alan Horsager(2014) Episona. Available at: https://www.episona.com/3-examples-transgenerational-epigenetic-inheritance/ (last accessed 18 Nov 2015)</ref>. It is reconstructed between generations. The methylation marks are supposed to be converted to hydroxymethylation which will be diluted as the cell divides<ref>University of Cambridge (25 Jan 2013) Available at: http://www.cam.ac.uk/research/news/scientists-discover-how-epigenetic-information-could-be-inherited (last accessed 18 Nov 2015)</ref>. Now, however, incomplete removal of epigenomes in specific genes have been found, suggesting that certain gene profiles are inherited epigenetically<ref name="[3]">Utahedu. 3. Utahedu. [Online]. Available from: http://learn.genetics.utah.edu/content/epigenetics/ [Accessed 20 November 2015].</ref>. Heritability of epigenetic modification has been observed in studies with mice. One such study revealed the transgenerational inheritance of the yellow coat colour phenotype in mice, resulting from the incomplete erasure of methylation marks when a silenced Avy allele is passed down through the female germline<ref>Morgan H, Sutherland H et al. Epigenetic inheritance at the agouti locus in the mouse. Nature Genetics 1999; 23(3)</ref>.  

Latest revision as of 21:36, 9 December 2018

Epigenetics is the study of changes to the genome and the heritability of said alterations. Gene expression within an organism can be altered by changes to the genome, without the DNA sequence itself being changed, in response to its environment. This essentially results in a change in the phenotype without a change to the genotype.

This is mainly caused by the addition of specific chemical groups on to the genome, which can promote or inhibit the transcription of genes into polypeptides. An example of epigenetic change is DNA methylation, which is the addition of a methyl group to cytosine by methyltransferases. The methyl group is added to the C5 atom of a cytosine base in a CpG dinucleotide within the DNA. This methyl group originates from an S-adenosyl-L-methionine (SAM) molecule, and the process is catalysed by DNA methyltransferases (DNMTs)[1]. This methylation prevents the binding of transcription factors and therefore leads to a low rate of transcription of those genes. It is also due to positive feedback loops of gene regulatory proteins or to heritable modifications in chromatin[2]. The genome alterations are considered to be heritable, therefore the changes in gene expression of an organism may affect their offspring in subsequent generations[3]. In other words, parents' past experience could be passed on to the  next generation which will make them have better characteristics than their parents.

The epigenome is a structure that consists of a histone octamer which tightly wrapped DNA is coiled, this fundamental repeating subunit is called the nucleosome. Changes to the epigenome results in conformational changes in the geometry of the genome. This “highlights” specific parts of the DNA sequence thus affecting transcription and, therefore, gene expression. Different cells have different active genes despite having similar DNA sequences. For example, brain cells and liver cells contain the same DNA sequence yet the expressed active genes are different. These histone modifications resulting in epigenetic change can be caused by over 150 chemical reactions such as acetylation, methylation, ubiquitination and phosphorylation[4].

Methylation is the addition of a methyl group onto a cytosine base, this results in the condensing of the DNA-histone complex. Meaning that there's a smaller area for transcriptional factors to bind to the genome. Acetylation is the addition of an acetyl group to a DNA molecule, which enhances the molecules affinity for binding proteins to interact with specific sites in order to initiate gene transcription.

Formerly, it was assumed that for proper cellular development and distinction to occur in mammals, the epigenome was fully erased through a 'reprogramming' process which happens twice; once during gamete formation and once during conception[5]. It is reconstructed between generations. The methylation marks are supposed to be converted to hydroxymethylation which will be diluted as the cell divides[6]. Now, however, incomplete removal of epigenomes in specific genes have been found, suggesting that certain gene profiles are inherited epigenetically[7]. Heritability of epigenetic modification has been observed in studies with mice. One such study revealed the transgenerational inheritance of the yellow coat colour phenotype in mice, resulting from the incomplete erasure of methylation marks when a silenced Avy allele is passed down through the female germline[8].

References

  1. Herceg Z. Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors. Mutagenesis. 2007. 22(2), 91–103
  2. Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts and Peter Walter. (2008) Molecular Biology of The Cell, Fifth Edition, New York: Garland Science.
  3. Carey N. The epigenetics revolution. United Kingdom: Icon Books Ltd; 2012.
  4. Griffiths AJF, Wessler SR, Carroll SB, Doebley J. Introduction to genetic analysis, 11th ed. United States of America: W.H. Freeman and Company; 2015.
  5. Alan Horsager(2014) Episona. Available at: https://www.episona.com/3-examples-transgenerational-epigenetic-inheritance/ (last accessed 18 Nov 2015)
  6. University of Cambridge (25 Jan 2013) Available at: http://www.cam.ac.uk/research/news/scientists-discover-how-epigenetic-information-could-be-inherited (last accessed 18 Nov 2015)
  7. Utahedu. 3. Utahedu. [Online]. Available from: http://learn.genetics.utah.edu/content/epigenetics/ [Accessed 20 November 2015].
  8. Morgan H, Sutherland H et al. Epigenetic inheritance at the agouti locus in the mouse. Nature Genetics 1999; 23(3)
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