Cited by 305Genomics and Chromatin DynamicsEpigenetics and DNA MethylationGenetics and Neurodevelopmental Disorders

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Chromatin Compaction by Human MeCP2

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Georgel, Philippe T., Horowitz-Scherer, Rachel A., Adkins, Nick, Woodcock, Christopher L., Wade, Paul A., Hansen, Jeffrey C.·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m305308200

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Abstract

MeCP2 is a transcriptional repressor that contains an N-terminal methylated DNA-binding domain, a central transcription regulation domain, and a C-terminal domain of unknown function. Whereas current models of MeCP2 function evoke localized recruitment of histone deacetylases to specific methylated regions of the genome, it is unclear whether MeCP2 requires DNA methylation to bind to chromatin or whether MeCP2 binding influences chromatin structure in the absence of other proteins. To address these issues, we have characterized the complexes formed between MeCP2 and biochemically defined nucleosomal arrays. At molar ratios near 1 MeCP2/nucleosome, unmethylated nucleosomal arrays formed both extensively condensed ellipsoidal particles and oligomeric suprastructures. Furthermore, MeCP2-mediated chromatin compaction occurred in the absence of monovalent or divalent cations, in distinct contrast to all other known chromatin-condensing proteins. Analysis of specific missense and nonsense MeCP2 mutants indicated that the ability to condense chromatin resides in region(s) of the protein other than the methylated DNA-binding domain. These data demonstrate that MeCP2 assembles novel secondary chromatin structures independent of DNA modification and suggest that the ability of MeCP2 to silence chromatin may be related in part to its effects on large-scale chromatin organization.

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Authors: Georgel, P. T., Horowitz-Scherer, R. A., Adkins, N., Woodcock, C. L., Wade, P. A., & Hansen, J. C.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
University of Massachusetts Amherst (US)
Marshall University (US)
Emory University (US)
Corresponding author: Wade, Paul A.
Hansen, Jeffrey C.
ORCID: Georgel, Philippe T.
Wade, Paul A.
Hansen, Jeffrey C.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-08
Volume: 278
Issue: 34
Pages: 32181-32188
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m305308200
OpenAlex: W2042269850
Cited by: 305
References: 39
Citations by year: 2026: 2 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 7 · 2019: 7 · 2018: 10 · 2017: 14 · 2016: 16 · 2015: 18 · 2014: 14 · 2013: 20 · 2012: 14
FWCI: 5.99
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6269 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Collection of Biostatistics Research Archive (COBRA) (submittedVersion)
Funders: National Institutes of Health (5k22hd001238-02, 5r01gm043786-11)
National Institute of General Medical Sciences (GM 45916, GM43786)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (5K22HD01238)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: MeCP2, chromatin condensation, nucleosome arrays, chromatin silencing, transcriptional repression, chromatin organization
MeSH terms: Chromatin, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Humans, Recombinant Proteins, Repressor Proteins, Protein Structure, Secondary, DNA Methylation, Methyl-CpG-Binding Protein 2

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Chromatin Compaction by Human MeCP2

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