A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.
Nucleic Acids Res. 43, 5208-5220 (2015)
The chromatin remodeling complex NoRC, comprising the subunits SNF2h and TIP5/BAZ2A, mediates heterochromatin formation at major clusters of repetitive elements, including rRNA genes, centromeres and telomeres. Association with chromatin requires the interaction of the TAM (TIP5/ARBP/MBD) domain of TIP5 with noncoding RNA, which targets NoRC to specific genomic loci. Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins. However, the TAM domain exhibits an extended MBD fold with unique C-terminal extensions that constitute a novel surface for RNA binding. Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo. Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Remodeling Complex Norc; Nmr Chemical-shifts; Heterochromatin Formation; Methyl-cpg; Backbone Dynamics; Dipolar Couplings; Dna Methylation; Noncoding Rna; Proteins; C-13
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Language
english
Publication Year
2015
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2015
ISSN (print) / ISBN
0305-1048
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1362-4962
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Volume: 43,
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Pages: 5208-5220
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Oxford University Press
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Oxford
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503000-001
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Erfassungsdatum
2015-04-30