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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents



ID: 682212.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences
Authors:Gunther, K.; Rust, M.; Leers, J.; Boettger, T.; Scharfe, M.; Jarek, M.; Bartkuhn, M.; Renkawitz, R.
Date of Publication (YYYY-MM-DD):2013-03-01
Journal Abbrev.:Nucleic Acids Res
Volume:41
Issue / Number:5
Start Page:3010
End Page:3021
Audience:Not Specified
Abstract / Description:The heterogeneous collection of nucleosome remodelling and deacetylation (NuRD) complexes can be grouped into the MBD2- or MBD3-containing complexes MBD2-NuRD and MBD3-NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here, we show that MBD2-NuRD, in contrast to MBD3-NuRD, converts open chromatin with euchromatic histone modifications into tightly compacted chromatin with repressive histone marks. Genome-wide, a strong enrichment for MBD2 at methylated CpG sequences is found, whereas CpGs bound by MBD3 are devoid of methylation. MBD2-bound genes are generally lower expressed as compared with MBD3-bound genes. When depleting cells for MBD2, the MBD2-bound genes increase their activity, whereas MBD2 plus MBD3-bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes.
Free Keywords:Animals; Binding Sites; Cell Line; *CpG Islands; DNA Methylation; DNA-Binding Proteins/metabolism/*physiology; Epigenesis, Genetic; Euchromatin/metabolism; *Exons; Genome, Human; Humans; *Promoter Regions, Genetic; Protein Binding; Protein Isoforms/metabolism/physiology; Protein Transport; Rats; Transcription Initiation Site
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1362-4962 (Electronic) 0305-1048 (Linking) %R 10.1093/nar/gkt035
URL:http://www.ncbi.nlm.nih.gov/pubmed/23361464
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