经典：epigenetics文献抄读
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CpG dinucleotides are unequally distributed across the human genome. Since vast stretches of sequences are deficient for CpGs and are interspersed by CpG clusters, these are also defined as ‘‘CpG islands’’ (CpG-rich areas). They are mainly associated with promoter regions of genes and mostly remain unmethylated.
Starting from the mid-1990s’, there has been a steady growth in the number of laboratories and investigators involved in epigenetic research. In the words of Andrew Feinberg, epigenetics has been moving at the very “epicenter of modern medicine because it can help to explain the relationship between an individual’s genetic background, the environment, aging, and disease”.
The genomic information is the same in all our cells and during our entire lifespan, the epigenomic information varies from cell to cell and during the lifetime of the individual.
Important alterations encompassing epigenetic changes are DNA methylation, histone modifications and RNA-based mechanisms including those controlled by microRNAs (miRNA) and long intergenic non-coding RNAs (linc-RNA).
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Recently, a family of methyl-CpG binding proteins(MBD) has also been recognized that specifically bind to methylation marks, thereby contributing to transcriptional repression by recruiting histone-modifying proteins.
Epigenetics and CVD
What is Epigenetics
The term ‘‘epigenetics’’ refers to heritable changes in gene expression, which are not a result of changes in the DNA sequence, but rather due to alterations related to the packaging (thereby altering DNA accessibility) and/or translation of genetic information.
10
CpG island in CDH1 promoter region
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Methylation of cytosine in CpG islands is associated with transcriptional repression by impeding the binding of transcription factors to cis-DNA binding elements present in the promoter regions of genes.
Even though epigenetic variability of genetic information is part of normal development and differentiation, it also underlies exogenous stimuli, e.g., environment ,aging, diet, smoking or drug abuse.
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14wenku.baidu.com
Histone modifications
7
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DNA methylation plays an essential role in several epigenetic phenomena including genomic imprinting, X-chromosome inactivation and retroelement silencing.
DNA Methylation
In the mammalian genome the most widely appreciated epigenetic modification involves the covalent binding of a methyl group, termed DNA methylation, to the 5'-position of cytosine residues in the so-called CpG (Cytosine preceding Guanosine) dinucleotides.
CpG dinucleotides are unequally distributed across the human genome. Since vast stretches of sequences are deficient for CpGs and are interspersed by CpG clusters, these are also defined as ‘‘CpG islands’’ (CpG-rich areas). They are mainly associated with promoter regions of genes and mostly remain unmethylated.
Starting from the mid-1990s’, there has been a steady growth in the number of laboratories and investigators involved in epigenetic research. In the words of Andrew Feinberg, epigenetics has been moving at the very “epicenter of modern medicine because it can help to explain the relationship between an individual’s genetic background, the environment, aging, and disease”.
The genomic information is the same in all our cells and during our entire lifespan, the epigenomic information varies from cell to cell and during the lifetime of the individual.
Important alterations encompassing epigenetic changes are DNA methylation, histone modifications and RNA-based mechanisms including those controlled by microRNAs (miRNA) and long intergenic non-coding RNAs (linc-RNA).
12
Recently, a family of methyl-CpG binding proteins(MBD) has also been recognized that specifically bind to methylation marks, thereby contributing to transcriptional repression by recruiting histone-modifying proteins.
Epigenetics and CVD
What is Epigenetics
The term ‘‘epigenetics’’ refers to heritable changes in gene expression, which are not a result of changes in the DNA sequence, but rather due to alterations related to the packaging (thereby altering DNA accessibility) and/or translation of genetic information.
10
CpG island in CDH1 promoter region
11
Methylation of cytosine in CpG islands is associated with transcriptional repression by impeding the binding of transcription factors to cis-DNA binding elements present in the promoter regions of genes.
Even though epigenetic variability of genetic information is part of normal development and differentiation, it also underlies exogenous stimuli, e.g., environment ,aging, diet, smoking or drug abuse.
13
14wenku.baidu.com
Histone modifications
7
8
DNA methylation plays an essential role in several epigenetic phenomena including genomic imprinting, X-chromosome inactivation and retroelement silencing.
DNA Methylation
In the mammalian genome the most widely appreciated epigenetic modification involves the covalent binding of a methyl group, termed DNA methylation, to the 5'-position of cytosine residues in the so-called CpG (Cytosine preceding Guanosine) dinucleotides.