Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.

2.50
Hdl Handle:
http://hdl.handle.net/10033/299507
Title:
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Authors:
Günther, Katharina; Rust, Mareike; Leers, Joerg; Boettger, Thomas; Scharfe, Maren; Jarek, Michael; Bartkuhn, Marek; Renkawitz, Rainer
Abstract:
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.
Affiliation:
Institute for Genetics, Justus-Liebig-University, D35392 Giessen, Germany.
Citation:
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences. 2013, 41 (5):3010-21 Nucleic Acids Res.
Journal:
Nucleic acids research
Issue Date:
1-Mar-2013
URI:
http://hdl.handle.net/10033/299507
DOI:
10.1093/nar/gkt035
PubMed ID:
23361464
Type:
Article
Language:
en
ISSN:
1362-4962
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorGünther, Katharinaen_GB
dc.contributor.authorRust, Mareikeen_GB
dc.contributor.authorLeers, Joergen_GB
dc.contributor.authorBoettger, Thomasen_GB
dc.contributor.authorScharfe, Marenen_GB
dc.contributor.authorJarek, Michaelen_GB
dc.contributor.authorBartkuhn, Mareken_GB
dc.contributor.authorRenkawitz, Raineren_GB
dc.date.accessioned2013-08-22T14:30:57Z-
dc.date.available2013-08-22T14:30:57Z-
dc.date.issued2013-03-01-
dc.identifier.citationDifferential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences. 2013, 41 (5):3010-21 Nucleic Acids Res.en_GB
dc.identifier.issn1362-4962-
dc.identifier.pmid23361464-
dc.identifier.doi10.1093/nar/gkt035-
dc.identifier.urihttp://hdl.handle.net/10033/299507-
dc.description.abstractThe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Nucleic acids researchen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBinding Sitesen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshCpG Islandsen_GB
dc.subject.meshDNA Methylationen_GB
dc.subject.meshDNA-Binding Proteinsen_GB
dc.subject.meshEpigenesis, Geneticen_GB
dc.subject.meshEuchromatinen_GB
dc.subject.meshExonsen_GB
dc.subject.meshGenome, Humanen_GB
dc.subject.meshHumansen_GB
dc.subject.meshPromoter Regions, Geneticen_GB
dc.subject.meshProtein Bindingen_GB
dc.subject.meshProtein Isoformsen_GB
dc.subject.meshProtein Transporten_GB
dc.subject.meshRatsen_GB
dc.subject.meshTranscription Initiation Siteen_GB
dc.titleDifferential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.en
dc.typeArticleen
dc.contributor.departmentInstitute for Genetics, Justus-Liebig-University, D35392 Giessen, Germany.en_GB
dc.identifier.journalNucleic acids researchen_GB

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