Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription

P L Jones; G J Veenstra; P A Wade; D Vermaak; S U Kass; N Landsberger; J Strouboulis; A P Wolffe

doi:10.1038/561

Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription

P L Jones, G J Veenstra, P A Wade, D Vermaak, S U Kass, N Landsberger, J Strouboulis, A P Wolffe

Comprehensive Cancer Centre

Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD 20892, USA; Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Eye Institute, Bethesda, MD 20892, USA.

Research output: Contribution to journal › Article › peer-review

2314 Citations (Scopus)

Abstract

CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.

Original language	English
Pages (from-to)	187-91
Number of pages	5
Journal	Nature Genetics
Volume	19
Issue number	2
DOIs	https://doi.org/10.1038/561
Publication status	Published - Jun 1998

Keywords

Amino Acid Sequence
Animals
Binding Sites
Chromosomal Proteins, Non-Histone
DNA Methylation
DNA-Binding Proteins/metabolism
Histone Deacetylases/metabolism
Methyl-CpG-Binding Protein 2
Molecular Sequence Data
Repressor Proteins/metabolism
Saccharomyces cerevisiae Proteins
Transcription Factors/metabolism
Transcription, Genetic
Xenopus Proteins
Xenopus laevis

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10.1038/561

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title = "Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription",

abstract = "CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.",

keywords = "Amino Acid Sequence, Animals, Binding Sites, Chromosomal Proteins, Non-Histone, DNA Methylation, DNA-Binding Proteins/metabolism, Histone Deacetylases/metabolism, Methyl-CpG-Binding Protein 2, Molecular Sequence Data, Repressor Proteins/metabolism, Saccharomyces cerevisiae Proteins, Transcription Factors/metabolism, Transcription, Genetic, Xenopus Proteins, Xenopus laevis",

author = "Jones, {P L} and Veenstra, {G J} and Wade, {P A} and D Vermaak and Kass, {S U} and N Landsberger and J Strouboulis and Wolffe, {A P}",

year = "1998",

month = jun,

doi = "10.1038/561",

language = "English",

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pages = "187--91",

journal = "Nature Genetics",

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T1 - Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription

AU - Jones, P L

AU - Veenstra, G J

AU - Wade, P A

AU - Vermaak, D

AU - Kass, S U

AU - Landsberger, N

AU - Strouboulis, J

AU - Wolffe, A P

PY - 1998/6

Y1 - 1998/6

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AB - CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - Chromosomal Proteins, Non-Histone

KW - DNA Methylation

KW - DNA-Binding Proteins/metabolism

KW - Histone Deacetylases/metabolism

KW - Methyl-CpG-Binding Protein 2

KW - Molecular Sequence Data

KW - Repressor Proteins/metabolism

KW - Saccharomyces cerevisiae Proteins

KW - Transcription Factors/metabolism

KW - Transcription, Genetic

KW - Xenopus Proteins

KW - Xenopus laevis

U2 - 10.1038/561

DO - 10.1038/561

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SN - 1061-4036

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SP - 187

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JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription

Abstract

Keywords

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