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 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]
The epigenome is involved in regulating gene expression, development, tissue differentiation, and suppression of
Cancer
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
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):
- ChIP-Seq) identifies genome wide patterns of histone modifications using antibodies against the modifications.[15]
- 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]
- Chromatin Accessibility – DNase I hypersensitive sites Sequencing (DNase-Seq) uses the DNase I enzyme to find open or accessible regions in the genome.
- Gene Expression – RNA-Seq and expression arrays identify expression levels or protein coding genes.
- 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
- ^
Bernstein BE, Meissner A, Lander ES (February 2007). "The mammalian epigenome". Cell. 128 (4): 669–681. PMID 17320505.
- PMID 7031747.
- ^ PMID 33494932.
- PMID 36638792.
- ^ "Human Epigenome Project". Archived from the original on 2011-07-16. Retrieved 2011-06-29.
- PMID 21507501.
- PMID 24091454.
- PMID 20130607.
- PMID 20162836.
- PMID 23613677.
- ^ "BioNews - Human Epigenome project launched" Archived 2010-12-28 at the Wayback Machine.
- ^ "France: Human epigenome consortium takes first steps" Archived 2015-07-08 at the Wayback Machine. 5 March 2010.
- ^ Eurice GmbH. "About IHEC".
- PMID 24592273.
- PMID 23333102.
- PMID 20852635.
External links
- Reference Epigenome Mapping Consortium Homepage
- NCBI Epigenomics Hub
- NCBI Gene Expression Omnibus Epigenomics
- The Human Epigenome Atlas
- Roadmap Epigenomics Visualization Hub
- Roadmap Epigenomics Visualization Hub (load track hub)
- Human Epigenome Browser at Washington University
- Epigenome Browser UCSC mirror Archived 2021-02-14 at the Wayback Machine
- Human Epigenome Project
- Cancer Research