CpG Islands

DNA methylation occurs almost exclusively on cytosines within CpG dinucleotides, which are found in the genome at approximately 20% of the predicted frequency, and the majority (>70%) of CpG dinucleotides are methylated. However, regions of CpG density, termed CpG islands, occur in the promoter regions of numerous genes proximal to their transcription start site, and/or in sequences adjacent to the promoter region (like exon 1). It has been suggested that up to 50% of all human genes may contain a promoter CpG island (Figure 1-3). These CpG islands are conventionally defined as ≥200 base pairs with ≥50% G+C and ≥0.6 CpG observed/CpG expected, although a more rigorous definition (≥200 base pairs with ≥60% G+C and ≥0.7 CpG observed/CpG expected) has been proposed. Some studies have suggested that large CpG islands are not required for sensitivity of gene promoters to methylation-dependent silencing. Rather, other regions of CpG density can behave like classically defined CpG islands. Most promoter CpG islands are unmethylated in normal tissues, but may become methylated in various pathological conditions. Distinct patterns of DNA methylation are found in the genomes of cells under different physiological conditions and in development. During most developmental stages DNA is heavily methylated. However, promoters and other regulatory regions of housekeeping genes are largely unmethylated in most cell types, and tissue-specific expressed genes are unmethylated only in the cell types where these genes are transcriptionally active.

 

DNA methylation is what occurs when methyl groups, an epigenetic factor found in some dietary sources, can tag DNA and activate or repress genes. Histones are proteins around which DNA can wind for compaction and gene regulation.

 

Histone modification occurs when the binding of epigenetic factors to histone “tails” alters the extent to which DNA is wrapped around histones and the availability of genes in the DNA to be activated.

All of these factors and processes can have an effect on people’s health and influence their health possibly resulting in cancer, autoimmune disease, mental disorders, or diabetes among other illnesses.

 

 

Content 4

Significance

Epigenetic modifications are crucial for packaging and interpreting the genome under the influence of physiological factors .  Epigenetics become a central issue in biological studies of development and disease [3, 7-11].  In recent years, there have been rapid advancees in the understanding of epigenetic mechanisms [12-14], which include histone modifications [4-6, 15], DNA methylation [10, 11, 16, 18], small and non-coding RNAs [20, 56], and chromatin architecture [13, 15, 21].  These mechanisms, in addition to other transcriptional regulationary events [15, 17], ultimately regulate gene activity and expression during development and differentiation, or in response to environmental stimuli [16, 17].

Epigenetic research can help explain how cells carrying identical DNA differentiate into different cell types, and how they maintain differentiated cellular states [14, 17].  Epigenetics is thus considered a bridge between genotype and phenotype [1-3, 7, 9].

While epigenetics refers to the changes of single genes or sets of genes, the term epigenome reflects the overall epigenetic state of a cell, and refers to global analyses of epigenetic markers across the entire genome [3, 14].  It is therefore critically important to map the epigenetic modification patterns or profile the epigenome in a given cell, which then can be used as epigenetic biomarkers for clinical prediction, diagnosis, and therapeutic development [8, 11, 18, 45].  International human epigenome projects are currently working to catalog all the epigenetic markers in all major tissues across the entire genome.  The resulting reference maps will usher in epigenetics as an exciting new era of medical science [14].  As an example of the research community's commitment to classifying epigenetic markers, the National Institutes of Health (NIH) has recently launched a $190 million research effort to learn more about epigenetics.

[histone modifications, with emphasis on their dynamic interactions within the chromatin environment to form the complex epigenetic mechanisms that orchestrate the regulation of genes at the molecular level .]
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  1. [Functionally, the patterns of epigenetic modifications serve as epigenetic markers to represent gene activity and expression as well as chromatin state.]???

Epigenetic alterations differ from genetic alterations in that they arise more frequently, are reversible, and occur at defined regions of specific genes. Epigenetics explains how the same genotype can produce different phenotypes, such as in the case of monozygotic twins. Epigenetic information is stored as chemical modifications to (i) the histone proteins that package the genome and (ii) cytosines within the sequence of the DNA. These chemical changes regulate DNA accessibility and directly influence how the genome is expressed throughout different developmental stages, across different tissue and cell types, and in various disease states. Many epigenomic modifications affect DNA, RNA, and protein, but DNA methylation, histone modifications, chromatin remodeling factors, and noncoding RNAs are among the most well-studied epigenetic mechanisms. Numerous epigenomic processes function together to establish and preserve the global or site-specific open or closed chromatin states that ultimately determine whether a gene is active or inactive.

Epigenetic alterations differ from genetic alterations in that they arise more frequently, are reversible, and occur at defined regions of specific genes. Epigenetics explains how the same genotype can produce different phenotypes, such as in the case of monozygotic twins. Epigenetic information is stored as chemical modifications to (i) the histone proteins that package the genome and (ii) cytosines within the sequence of the DNA. These chemical changes regulate DNA accessibility and directly influence how the genome is expressed throughout different developmental stages, across different tissue and cell types, and in various disease states. Many epigenomic modifications affect DNA, RNA, and protein, but DNA methylation, histone modifications, chromatin remodeling factors, and noncoding RNAs are among the most well-studied epigenetic mechanisms. Numerous epigenomic processes function together to establish and preserve the global or site-specific open or closed chromatin states that ultimately determine whether a gene is active or inactive.

 

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