Epigenome

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In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; 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]

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Epigenome Epigenome.png
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.

Aging

The idea that DNA damage drives aging by compromising transcription and DNA replication has been widely supported since it was initially developed the 1980s. [2] In recent decades, evidence has accumulated supporting the additional idea that DNA damage and repair elicit widespread epigenome alterations that also contribute to aging (e.g. [3] [4] ). Such epigenome changes include age-related changes in the patterns of DNA methylation and histone modification. [3]

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. [5] Advances in sequencing technology now allow for assaying genome-wide epigenomic states by multiple molecular methodologies. [6] Micro- and nanoscale devices have been constructed or proposed to investigate the epigenome. [7]

An international effort to assay reference epigenomes commenced in 2010 in the form of the International Human Epigenome Consortium (IHEC). [8] [9] [10] [11] IHEC members aim to generate at least 1,000 reference (baseline) human epigenomes from different types of normal and disease-related human cell types. [12] [13] [14]

Roadmap epigenomics project

One goal of the NIH Roadmap Epigenomics Project Archived 2021-04-08 at the Wayback Machine 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. [15]
  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. [16]
  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

Related Research Articles

Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair. Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.

The Epigenomics database at the National Center for Biotechnology Information was a database for whole-genome epigenetics data sets. It was retired on 1 June 2016.

H3K4me3 is an epigenetic modification to the DNA packaging protein Histone H3 that indicates tri-methylation at the 4th lysine residue of the histone H3 protein and is often involved in the regulation of gene expression. The name denotes the addition of three methyl groups (trimethylation) to the lysine 4 on the histone H3 protein.

H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein.

H3K9me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 9th lysine residue of the histone H3 protein and is often associated with heterochromatin.

Human epigenome is the complete set of structural modifications of chromatin and chemical modifications of histones and nucleotides. These modifications affect according to cellular type and development status. Various studies show that epigenome depends on exogenous factors.

H3K4me1 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the mono-methylation at the 4th lysine residue of the histone H3 protein and often associated with gene enhancers.

H3K36me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 36th lysine residue of the histone H3 protein and often associated with gene bodies.

H3K79me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 79th lysine residue of the histone H3 protein. H3K79me2 is detected in the transcribed regions of active genes.

H4K20me is an epigenetic modification to the DNA packaging protein Histone H4. It is a mark that indicates the mono-methylation at the 20th lysine residue of the histone H4 protein. This mark can be di- and tri-methylated. It is critical for genome integrity including DNA damage repair, DNA replication and chromatin compaction.

H3K14ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 14th lysine residue of the histone H3 protein.

H3K36ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 36th lysine residue of the histone H3 protein.

H3K36me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 36th lysine residue of the histone H3 protein.

H3K36me is an epigenetic modification to the DNA packaging protein Histone H3, specifically, the mono-methylation at the 36th lysine residue of the histone H3 protein.

H3R42me is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the mono-methylation at the 42nd arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R17me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 17th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R26me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 26th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R8me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 8th arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H3R2me2 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the di-methylation at the 2nd arginine residue of the histone H3 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

H4R3me2 is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the di-methylation at the 3rd arginine residue of the histone H4 protein. In epigenetics, arginine methylation of histones H3 and H4 is associated with a more accessible chromatin structure and thus higher levels of transcription. The existence of arginine demethylases that could reverse arginine methylation is controversial.

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. ↑ Gensler HL, Bernstein H (September 1981). "DNA damage as the primary cause of aging". Q Rev Biol. 56 (3): 279–303. doi:10.1086/412317. PMID   7031747.
  3. 1 2 Siametis A, Niotis G, Garinis GA (April 2021). "DNA Damage and the Aging Epigenome". J Invest Dermatol. 141 (4S): 961–967. doi:10.1016/j.jid.2020.10.006. PMID   33494932.
  4. ↑ Yang JH, Hayano M, Griffin PT, Amorim JA, Bonkowski MS, Apostolides JK, Salfati EL, Blanchette M, Munding EM, Bhakta M, Chew YC, Guo W, Yang X, Maybury-Lewis S, Tian X, Ross JM, Coppotelli G, Meer MV, Rogers-Hammond R, Vera DL, Lu YR, Pippin JW, Creswell ML, Dou Z, Xu C, Mitchell SJ, Das A, O'Connell BL, Thakur S, Kane AE, Su Q, Mohri Y, Nishimura EK, Schaevitz L, Garg N, Balta AM, Rego MA, Gregory-Ksander M, Jakobs TC, Zhong L, Wakimoto H, El Andari J, Grimm D, Mostoslavsky R, Wagers AJ, Tsubota K, Bonasera SJ, Palmeira CM, Seidman JG, Seidman CE, Wolf NS, Kreiling JA, Sedivy JM, Murphy GF, Green RE, Garcia BA, Berger SL, Oberdoerffer P, Shankland SJ, Gladyshev VN, Ksander BR, Pfenning AR, Rajman LA, Sinclair DA (January 2023). "Loss of epigenetic information as a cause of mammalian aging". Cell. 186 (2): 305–326.e27. doi:10.1016/j.cell.2022.12.027. PMC   10166133 . PMID   36638792.
  5. ↑ "Human Epigenome Project". Archived from the original on 2011-07-16. Retrieved 2011-06-29.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ "Time for the epigenome". Nature. 463 (7281): 587. February 2010. Bibcode:2010Natur.463Q.587.. doi: 10.1038/463587a . PMID   20130607.
  9. ↑ Abbott A (February 2010). "Project set to map marks on genome". Nature. 463 (7281): 596–7. doi: 10.1038/463596b . PMID   20162836.
  10. ↑ 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.
  11. ↑ "BioNews - Human Epigenome project launched" Archived 2010-12-28 at the Wayback Machine .
  12. ↑ "France: Human epigenome consortium takes first steps" Archived 2015-07-08 at the Wayback Machine . 5 March 2010.
  13. ↑ Eurice GmbH. "About IHEC".
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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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