DNA methylation and histone deacetylation in the control of gene expression: Basic biochemistry to human development and disease

A. El-Osta, A. P. Wolffe

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

DNA methylation is a major determinant in the epigenetic silencing of genes. The mechanisms underlying the targeting of DNA methylation and the subsequent repression of transcription are relevant to human development and disease, as well as for attempts at somatic gene therapy. The success of transgenic technologies in plants and animals is also compromised by DNA methylation-dependent silencing pathways. Recent biochemical experiments provide a mechanistic foundation for understanding the influence of DNA methylation on transcription. The DNA methyltransferase Dnmt1, and several methyl-CpG binding proteins, MeCP2, MBD2, and MBD3, all associate with histone deacetylase. These observations firmly connect DNA methylation with chromatin modifications. They also provide new pathways for the potential targeting of DNA methylation to repressive chromatin as well as the assembly of repressive chromatin on methylated DNA. Here we discuss the implications of the methylation-acetylation connection for human cancers and the developmental syndromes Fragile X and Rett, which involve a mistargeting of DNA methylation-dependent repression.

Original languageEnglish
Pages (from-to)63-75
Number of pages13
JournalGene Expression
Volume9
Issue number1-2
Publication statusPublished - 7 Dec 2000
Externally publishedYes

Keywords

  • 5-Aza 2'deoxycytidine
  • Chromatin remodeling
  • DNA methyltransferase
  • Fragile X syndrome
  • Histone deacetylase
  • Methyl-CpG binding proteins
  • p16(INK4)
  • Rett syndrome

Cite this

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title = "DNA methylation and histone deacetylation in the control of gene expression: Basic biochemistry to human development and disease",
abstract = "DNA methylation is a major determinant in the epigenetic silencing of genes. The mechanisms underlying the targeting of DNA methylation and the subsequent repression of transcription are relevant to human development and disease, as well as for attempts at somatic gene therapy. The success of transgenic technologies in plants and animals is also compromised by DNA methylation-dependent silencing pathways. Recent biochemical experiments provide a mechanistic foundation for understanding the influence of DNA methylation on transcription. The DNA methyltransferase Dnmt1, and several methyl-CpG binding proteins, MeCP2, MBD2, and MBD3, all associate with histone deacetylase. These observations firmly connect DNA methylation with chromatin modifications. They also provide new pathways for the potential targeting of DNA methylation to repressive chromatin as well as the assembly of repressive chromatin on methylated DNA. Here we discuss the implications of the methylation-acetylation connection for human cancers and the developmental syndromes Fragile X and Rett, which involve a mistargeting of DNA methylation-dependent repression.",
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DNA methylation and histone deacetylation in the control of gene expression : Basic biochemistry to human development and disease. / El-Osta, A.; Wolffe, A. P.

In: Gene Expression, Vol. 9, No. 1-2, 07.12.2000, p. 63-75.

Research output: Contribution to journalReview ArticleResearchpeer-review

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AU - El-Osta, A.

AU - Wolffe, A. P.

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AB - DNA methylation is a major determinant in the epigenetic silencing of genes. The mechanisms underlying the targeting of DNA methylation and the subsequent repression of transcription are relevant to human development and disease, as well as for attempts at somatic gene therapy. The success of transgenic technologies in plants and animals is also compromised by DNA methylation-dependent silencing pathways. Recent biochemical experiments provide a mechanistic foundation for understanding the influence of DNA methylation on transcription. The DNA methyltransferase Dnmt1, and several methyl-CpG binding proteins, MeCP2, MBD2, and MBD3, all associate with histone deacetylase. These observations firmly connect DNA methylation with chromatin modifications. They also provide new pathways for the potential targeting of DNA methylation to repressive chromatin as well as the assembly of repressive chromatin on methylated DNA. Here we discuss the implications of the methylation-acetylation connection for human cancers and the developmental syndromes Fragile X and Rett, which involve a mistargeting of DNA methylation-dependent repression.

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KW - Fragile X syndrome

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