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Epigenome

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An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.[1]

Epigenome

The epigenome is involved in regulating gene expression, development, tissue differentiation, and suppression of transposable elements. Unlike the underlying genome, which remains largely static within an individual, the epigenome can be dynamically altered by environmental conditions.

Cancer

Epigenetics is a currently active topic in cancer research. Human tumors undergo a major disruption of DNA methylation and histone modification patterns. The aberrant epigenetic landscape of the cancer cell is characterized by a global genomic hypomethylation, CpG island promoter hypermethylation of tumor suppressor genes, an altered histone code for critical genes and a global loss of monoacetylated and trimethylated histone H4.

Epigenome research projects

As a prelude to a potential Human Epigenome Project, the Human Epigenome Pilot Project aims to identify and catalogue Methylation Variable Positions (MVPs) in the human genome.[2] Advances in sequencing technology now allow for assaying genome-wide epigenomic states by multiple molecular methodologies.[3] Micro- and nanoscale devices have been constructed or proposed to investigate the epigenome.[4]

An international effort to assay reference epigenomes commenced in 2010 in the form of the International Human Epigenome Consortium (IHEC).[5][6][7][8] IHEC members aim to generate at least 1,000 reference (baseline) human epigenomes from different types of normal and disease-related human cell types.[9][10][11]

Roadmap epigenomics project

One goal of the NIH Roadmap Epigenomics Project is to generate human reference epigenomes from normal, healthy individuals across a large variety of cell lines, primary cells, and primary tissues. Data produced by the project, which can be browsed and downloaded from the Human Epigenome Atlas, fall into five types that assay different aspects of the epigenome and outcomes of epigenomic states (such as gene expression):

  1. Histone Modifications – Chromatin Immunoprecipitation Sequencing (ChIP-Seq) identifies genome wide patterns of histone modifications using antibodies against the modifications.[12]
  2. DNA Methylation – Whole Genome Bisulfite-Seq, Reduced Representation Bisulfite-Seq (RRBS), Methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq), and Methylation-sensitive Restriction Enzyme Sequencing (MRE-Seq) identify DNA methylation across portions of the genome at varying levels of resolution down to basepair level.[13]
  3. Chromatin Accessibility – DNase I hypersensitive sites Sequencing (DNase-Seq) uses the DNase I enzyme to find open or accessible regions in the genome.
  4. Gene Expression – RNA-Seq and expression arrays identify expression levels or protein coding genes.
  5. Small RNA Expression – smRNA-Seq identifies expression of small noncoding RNA, primarily miRNAs.

Reference epigenomes for healthy individuals will enable the second goal of the Roadmap Epigenomics Project, which is to examine epigenomic differences that occur in disease states such as Alzheimer's disease.

See also

References

  1. ^ Bernstein BE, Meissner A, Lander ES (February 2007). "The mammalian epigenome". Cell. 128 (4): 669–681. doi:10.1016/j.cell.2007.01.033. PMID 17320505.
  2. ^ "Human Epigenome Project". Archived from the original on 2011-07-16. Retrieved 2011-06-29.
  3. ^ Milosavljevic A (June 2011). "Emerging patterns of epigenomic variation". Trends in Genetics. 27 (6): 242–250. doi:10.1016/j.tig.2011.03.001. PMC 3104125. PMID 21507501.
  4. ^ Aguilar CA, Craighead HG (October 2013). "Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics". Nature Nanotechnology. 8 (10): 709–718. Bibcode:2013NatNa...8..709A. doi:10.1038/nnano.2013.195. PMC 4072028. PMID 24091454.
  5. ^ "Time for the epigenome". Nature. 463 (7281): 587. February 2010. Bibcode:2010Natur.463Q.587.. doi:10.1038/463587a. PMID 20130607.
  6. ^ Abbott A (February 2010). "Project set to map marks on genome". Nature. 463 (7281): 596–597. doi:10.1038/463596b. PMID 20162836.
  7. ^ Bae JB (March 2013). "Perspectives of international human epigenome consortium". Genomics & Informatics. 11 (1): 7–14. doi:10.5808/GI.2013.11.1.7. PMC 3630389. PMID 23613677.
  8. ^ "BioNews - Human Epigenome project launched".
  9. ^ "France: Human epigenome consortium takes first steps" Archived 2015-07-08 at the Wayback Machine. 5 March 2010.
  10. ^ Eurice GmbH. "About IHEC".
  11. ^ Kanai Y, Arai E (2014). "Multilayer-omics analyses of human cancers: exploration of biomarkers and drug targets based on the activities of the International Human Epigenome Consortium". Frontiers in Genetics. 5: 24. doi:10.3389/fgene.2014.00024. PMC 3924033. PMID 24592273.
  12. ^ Zhu J, Adli M, Zou JY, Verstappen G, Coyne M, Zhang X, et al. (January 2013). "Genome-wide chromatin state transitions associated with developmental and environmental cues". Cell. 152 (3): 642–654. doi:10.1016/j.cell.2012.12.033. PMC 3563935. PMID 23333102.
  13. ^ Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C, Downey SL, et al. (October 2010). "Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications". Nature Biotechnology. 28 (10): 1097–1105. doi:10.1038/nbt.1682. PMC 2955169. PMID 20852635.
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