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An epigenome consists of a record of the chemical changes to the DNA and
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
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 Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
and changes to the function of the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
. The epigenome is involved in regulating gene expression, development, tissue differentiation, and suppression of
transposable elements A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Trans ...
. Unlike the underlying genome, which remains largely static within an individual, the epigenome can be dynamically altered by environmental conditions.


Cancer

Epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
is a currently active topic in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
research. Human
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s undergo a major disruption of
DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
and
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
modification patterns. The aberrant epigenetic landscape of the cancer cell is characterized by a global genomic hypomethylation,
CpG island The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG isl ...
promoter hypermethylation of tumor suppressor
genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
, an altered
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
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 In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
. Advances in sequencing technology now allow for assaying genome-wide epigenomic states by multiple molecular methodologies. Micro- and nanoscale devices have been constructed or proposed to investigate the epigenome. An international effort to assay reference epigenomes commenced in 2010 in the form of the
International Human Epigenome Consortium The International Human Epigenome Consortium (IHEC) is a scientific organization, founded in 2010, that helps to coordinate global efforts in the field of Epigenomics. The initial goal was to generate at least 1,000 reference (baseline) human ep ...
(IHEC). IHEC members aim to generate at least 1,000 reference (baseline) human epigenomes from different types of normal and disease-related human
cell types A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cells, ...
.Eurice GmbH
"About IHEC"


Roadmap epigenomics project

One goal of th
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 th
Human Epigenome Atlas
fall into five types that assay different aspects of the epigenome and outcomes of epigenomic states (such as gene expression): #
Histone Modifications In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are w ...
– Chromatin Immunoprecipitation Sequencing (
ChIP-Seq ChIP-sequencing, also known as ChIP-seq, is a method used to analyze protein interactions with DNA. ChIP-seq combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to identify the binding sites of DNA-associated prote ...
) identifies genome wide patterns of histone modifications using antibodies against the modifications. #
DNA Methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
– 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. # Chromatin Accessibility
DNase I hypersensitive site In genetics, DNase I hypersensitive sites (DHSs) are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it ac ...
s Sequencing (
DNase-Seq DNase-seq (DNase I hypersensitive sites sequencing) is a method in molecular biology used to identify the location of regulatory regions, based on the genome-wide sequencing of regions sensitive to cleavage by DNase I. FAIRE-Seq is a successor of D ...
) uses the DNase I enzyme to find open or accessible regions in the genome. #
Gene Expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
RNA-Seq RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing c ...
and expression arrays identify expression levels or protein coding genes. # Small RNA Expression – smRNA-Seq identifies expression of small noncoding RNA, primarily
miRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s. 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 Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
.


See also

*
Epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
*
Epigenome editing Epigenome editing or Epigenome engineering is a type of genetic engineering in which the epigenome is modified at specific sites using engineered molecules targeted to those sites (as opposed to whole-genome modifications). Whereas gene editing inv ...
*
Human epigenome Human epigenome is the complete set of structural modifications of chromatin and chemical modifications of histones and nucleotides (such as cytosine methylation). These modifications affect t according to cellular type and development status. Vari ...
*
NCBI Epigenomics 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. The Epigenomics database The Epigenomics database of the National Center for Biotech ...


References


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
{{Webarchive, url=https://web.archive.org/web/20210214005034/http://www.epigenomebrowser.org/ , date=2021-02-14
Human Epigenome Project

Cancer Research
Epigenetics