DNA Methylation and Histone Deacetylation in the Control of Gene Expression: Basic Biochemistry to Human Development and Disease

Authors: EL-OSTA A.; WOLFFE A.P.

Source: Gene Expression, Volume 9, Numbers 1-2, 2001 , pp. 63-75(13)

Publisher: Cognizant Communication Corporation

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.

Keywords: Rett syndrome Fragile X syndrome Methyl-CpG binding proteins DNA methyltransferase Histone deacetylase Chromatin remodeling p161NK4 5-aza 2deoxycytidine

Language: English

Document Type: Research article

Affiliations: 1: Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Bethesda, MD 20892-5431

Publication date: 2001-01-01

• The Molecular and Cellular Biology area of Gene Expression covers all aspects of the gene including it structure, functions, and regulation in prokaryotes, eukaryotes, and viruses; molecular and cell biological aspects of cell growth and development, chromatin structure and function. These include topics such as DNA replication, DNA repair, gene transcription, transcriptional control, RNA processing, posttranscriptional control, oncogenes, molecular mechanisms of action of hormones, molecular mechanism of cellular differentiation, growth and development, protein synthesis, and posttranslational control.
  The Molecular and Cellular Neuroscience area of Gene Expression covers all aspects of gene expression as described but is devoted exclusively to the nervous system in health and disease. Topics include studies of neurogenesis, development, aging, and neurodegeneration. Complex neural systems, motor control, special senses, and higher cortical function, when viewed from the perspective of gene expression, are appropriate for the journal. Research related to molecular mechanisms of drug tolerance, dependence, and withdrawal are solicited. Manuscripts on state-of-the-art methods and protocols for molecular profiling of neuronal structure and function are welcome.

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• In this Subject: Biotechnology ,  Genetics
• By this author: EL-OSTA A. ;  WOLFFE A.P.

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