5agq
From Proteopedia
Solution structure of the TAM domain of human TIP5 BAZ2A involved in epigenetic regulation of rRNA genes
Structural highlights
FunctionBAZ2A_HUMAN Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity). Publication Abstract from PubMedThe 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. A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.,Anosova I, Melnik S, Tripsianes K, Kateb F, Grummt I, Sattler M Nucleic Acids Res. 2015 Apr 27. pii: gkv365. PMID:25916849[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Anosova I | Grummt I | Kateb F | Melnik S | Sattler M | Tripsianes K
