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Anosova, I. ; Melnik, S.* ; Tripsianes, K. ; Kateb, F. ; Grummt, I.* ; Sattler, M.

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)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Remodeling Complex Norc; Nmr Chemical-shifts; Heterochromatin Formation; Methyl-cpg; Backbone Dynamics; Dipolar Couplings; Dna Methylation; Noncoding Rna; Proteins; C-13
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Band: 43, Heft: 10, Seiten: 5208-5220 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed