气候变化领域集成服务门户(CCPortal): MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion

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DOI	10.1126/science.abd5581
	MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion
	Ibrahim A.; Papin C.; Mohideen-Abdul K.; Gras S.L.; Stoll I.; Bronner C.; Dimitrov S.; Klaholz B.P.; Hamiche A.
发表日期	2021
ISSN	0036-8075
卷号	372 期号:6549
英文摘要	The Rett syndrome protein MeCP2 was described as a methyl-CpG-binding protein, but its exact function remains unknown. Here we show that mouse MeCP2 is a microsatellite binding protein that specifically recognizes hydroxymethylated CA repeats. Depletion of MeCP2 alters chromatin organization of CA repeats and lamina-associated domains and results in nucleosome accumulation on CA repeats and genome-wide transcriptional dysregulation. The structure of MeCP2 in complex with a hydroxymethylated CA repeat reveals a characteristic DNA shape, with considerably modified geometry at the 5-hydroxymethylcytosine, which is recognized specifically by Arg133, a key residue whose mutation causes Rett syndrome. Our work identifies MeCP2 as a microsatellite DNA binding protein that targets the 5hmC-modified CA-rich strand and maintains genome regions nucleosome-free, suggesting a role for MeCP2 dysfunction in Rett syndrome. © 2021 American Association for the Advancement of Science. All rights reserved.
英文关键词	5 hydroxymethylcytosine; arginine; asparagine; chloroform; cytosine; dinucleotide; DNA (cytosine 5) methyltransferase; DNA (cytosine 5) methyltransferase 1; DNA methyltransferase 3A; DNA methyltransferase 3B; flag peptide; genomic DNA; glycine; mercaptoethanol; methionine; methyl CpG binding protein 2; micrococcal nuclease; microsatellite DNA; mutant protein; nucleic acid binding protein; oligonucleotide; peptide; phenol; phenylalanine; polyhistidine tag; serine; threonine; tryptophan; unclassified drug; valine; 5 methylcytosine; 5-hydroxymethylcytosine; cytosine; Mecp2 protein, mouse; methyl CpG binding protein 2; microsatellite DNA; protein binding; chemical binding; DNA; genome; protein; rodent; adult; affinity chromatography; animal cell; animal tissue; Article; baculovirus expression system; binding affinity; binding site; bioinformatics; brain development; brain tissue; CA repeat; cell invasion; cell isolation; centrifugation; chemical modification; chromatin; chromatin immunoprecipitation; chromatin structure; comparative study; conformational transition; controlled study; CpG island; crystal structure; crystallization; differential expression analysis; DNA binding; DNA immunoprecipitation; DNA methylation; DNA sequence; DNA structure; down regulation; ectopic expression; embryo; enzyme activity; Escherichia coli; female; fibroblast; gel mobility shift assay; gene expression; gene mutation; gene ontology; genetic transfection; genome; genome-wide association study; geometry; hemagglutination; high performance liquid chromatography; high throughput sequencing; hydrogen bond; illumina sequencing; image analysis; immunoprecipitation; in vitro study; in vivo study; inhibition constant; ion exchange chromatography; mass spectrometry; mental disease; methylation; molecular cloning; molecular genetics; molecular recognition; mouse; neurite outgrowth; nonhuman; nuclear magnetic resonance; nucleosome; Protein Data Bank; protein DNA interaction; protein purification; pull-down assay; real time polymerase chain reaction; Rett syndrome; RNA sequence; Sf9 cell line; short tandem repeat; size exclusion chromatography; transcription regulation; transcriptomics; upregulation; viral gene delivery system; Western blotting; whole genome bisulfite sequencing; animal; cell culture; chemistry; conformation; dinucleotide repeat; embryonic stem cell; frontal lobe; genetic transcription; genetics; metabolism; nerve cell; nucleosome; oxidation reduction reaction; protein domain; ultrastructure; 5-Methylcytosine; Animals; Cells, Cultured; Chromatin; Cytosine; Dinucleotide Repeats; DNA Methylation; Embryonic Stem Cells; Fibroblasts; Frontal Lobe; Methyl-CpG-Binding Protein 2; Mice; Microsatellite Repeats; Neurons; Nucleic Acid Conformation; Nucleosomes; Oxidation-Reduction; Protein Binding; Protein Domains; Rett Syndrome; Transcription, Genetic
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/244114
作者单位	Institute of Genetics and of Molecular and Cellular Biology (IGBMC), Illkirch, 67400, France; Department of Functional Genomics and Cancer, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, 67404, France; Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, 67404, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, 67404, France; Université de Strasbourg, Illkirch, 67404, France; Biotechnology Research Center (BTRC), Tripoli, 30303, Libyan Arab Jamahiriya; Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, Illkirch, 67404, France; Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé - Allée des Alpes, La Tronche, 38700, France; Roumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, 1113, Bulgaria; Center of Excellence in Bionanoscience Research, King Abdulaziz University (KAU), ...
推荐引用方式 GB/T 7714	Ibrahim A.,Papin C.,Mohideen-Abdul K.,et al. MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion[J],2021,372(6549).
APA	Ibrahim A..,Papin C..,Mohideen-Abdul K..,Gras S.L..,Stoll I..,...&Hamiche A..(2021).MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion.Science,372(6549).
MLA	Ibrahim A.,et al."MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion".Science 372.6549(2021).