Epigenome

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 epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.[1]

The epigenome is involved in regulating gene expression, development, tissue differentiation, and suppression of transposable elements. Unlike the underlying genome which is largely static within an individual, the epigenome can be dynamically altered by environmental conditions.[2]

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.[3] Advances in sequencing technology now allow for assaying genome-wide epigenomic states by multiple molecular methodologies.[4] Micro- and nanoscale devices have been constructed or proposed to investigate the epigenome.[5]

An international effort to assay reference epigenomes commenced in 2010 in the form of the International Human Epigenome Consortium (IHEC).[6][7][8][9] IHEC members aim to generate at least 1,000 reference (baseline) human epigenomes from different types of normal and disease-related human cell types.[10][11][12]

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.[13]
  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.[14]
  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.

Caution

Due to the early stages of epigenetics as a science and to the sensationalism surrounding it, surgical oncologist David Gorski and geneticist Adam Rutherford caution against the drawing and proliferation of false and pseudoscientific conclusions from new age authors such as Deepak Chopra and Bruce Lipton.[15][16]

See also

References

  1. ↑ Bernstein, Bradley E.; Meissner, Alexander; Lander,Eric S. (February 2007). "The Mammalian Epigenome". Cell. 128 (4): 669–681. doi:10.1016/j.cell.2007.01.033. PMID 17320505. Retrieved 19 December 2011.
  2. ↑ Conley, A.B., King Jordan, I. (2012). Endogenous Retroviruses and the Epigenome. In: Witzany, G. (ed). Viruses: Essential Agents of Life, Springer, Dordrecht, pp. 309-323.
  3. ↑ Human Epigenome Project
  4. ↑ Milosavljevic, Aleksandar (June 2011). "Emerging patterns of epigenomic variation". Trends in Genetics. 27: 242–250. doi:10.1016/j.tig.2011.03.001.
  5. ↑ Aguilar, Carlos; Craighead, Harold (October 4, 2013). "Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics". Nature Nanotechnology. 8 (10): 709–718. doi:10.1038/nnano.2013.195.
  6. ↑ "Time for the epigenome : Article : Nature".
  7. ↑ Project set to map marks on genome: Nature 463: 596-597 (2010) doi:10.1038/463596b
  8. ↑ "Perspectives of International Human Epigenome Consortium".
  9. ↑ "BioNews - Human Epigenome project launched".
  10. ↑ "France: Human epigenome consortium takes first steps". 5 March 2010.
  11. ↑ Eurice GmbH. "About IHEC".
  12. ↑ "Frontiers | Multilayer-omics analyses of human cancers: exploration of biomarkers and drug targets based on the activities of the International Human Epigenome Consortium | Epigenomics and Epigenetics". Frontiers.
  13. ↑ Zhu, J.; et al. (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. PMID 23333102.
  14. ↑ Harris, R Alan; Wang, Ting; Coarfa, Cristian; Nagarajan, Raman P; Hong, Chibo; Downey, Sara L; et al. (September 19, 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.
  15. ↑ "Beware the pseudo gene genies". The Guardian.
  16. ↑ "Epigenetics: It doesn’t mean what quacks think it means". Science-Based Medicine.

External links

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