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.
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 ProjectArchived 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):
Histone Modifications – Chromatin Immunoprecipitation Sequencing (
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]
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.
^Gensler HL, Bernstein H (September 1981). "DNA damage as the primary cause of aging". Q Rev Biol. 56 (3): 279–303.
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10.1086/412317.
PMID7031747.
^
abSiametis 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.
PMID33494932.
^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.
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