Connections between epigenetic gene silencing and human disease

Timothy J Moss; Lori L Wallrath

doi:10.1016/j.mrfmmm.2006.05.038

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Connections between epigenetic gene silencing and human disease

Journal article

Open access

Peer reviewed

Connections between epigenetic gene silencing and human disease

Timothy J Moss and Lori L Wallrath

Mutation research, Vol.618(1-2), pp.163-174

05/01/2007

DOI: 10.1016/j.mrfmmm.2006.05.038

PMCID: PMC1892579

PMID: 17306846

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https://www.ncbi.nlm.nih.gov/pmc/articles/1892579View

Open Access

Abstract

Alterations in epigenetic gene regulation are associated with human disease. Here, we discuss connections between DNA methylation and histone methylation, providing examples in which defects in these processes are linked with disease. Mutations in genes encoding DNA methyltransferases and proteins that bind methylated cytosine residues cause changes in gene expression and alterations in the patterns of DNA methylation. These changes are associated with cancer and congenital diseases due to defects in imprinting. Gene expression is also controlled through histone methylation. Altered levels of methyltransferases that modify lysine 27 of histone H3 (K27H3) and lysine 9 of histone H3 (K9H3) correlate with changes in Rb signaling and disruption of the cell cycle in cancer cells. The K27H3 mark recruits a Polycomb complex involved in regulating stem cell pluripotency, silencing of developmentally regulated genes, and controlling cancer progression. The K9H3 methyl mark recruits HP1, a structural protein that plays a role in heterochromatin formation, gene silencing, and viral latency. Cells exhibiting altered levels of HP1 are predicted to show a loss of silencing at genes regulating cancer progression. Gene silencing through K27H3 and K9H3 can involve histone deacetylation and DNA methylation, suggesting cross talk between epigenetic silencing systems through direct interactions among the various players. The reversible nature of these epigenetic modifications offers therapeutic possibilities for a wide spectrum of disease.

Chromatin - metabolism

Chromosomal Proteins, Non-Histone - metabolism

Epigenesis, Genetic

Humans

Methyltransferases - metabolism

Gene Silencing

DNA (Cytosine-5-)-Methyltransferases - genetics

DNA Methylation

Animals

Models, Biological

Models, Genetic

Histones - metabolism

Mutation

Repressor Proteins - metabolism

Details

Title: Subtitle: Connections between epigenetic gene silencing and human disease
Creators: Timothy J Moss - Department of Biochemistry, 3136 MERF, University of Iowa, Iowa City, IA 52242, USA
Lori L Wallrath
Resource Type: Journal article
Publication Details: Mutation research, Vol.618(1-2), pp.163-174
DOI: 10.1016/j.mrfmmm.2006.05.038
PMID: 17306846
PMCID: PMC1892579
NLM abbreviation: Mutat Res
ISSN: 0027-5107
eISSN: 1873-135X
Publisher: Netherlands
Grant note: R01 GM061513 / NIGMS NIH HHS T32 GM007337 / NIGMS NIH HHS GM61513 / NIGMS NIH HHS
Language: English
Date published: 05/01/2007
Academic Unit: Biochemistry and Molecular Biology; University College Courses
Record Identifier: 9984025393802771

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