TY - JOUR
T1 - A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes
AU - Anosova, Irina
AU - Melnik, Svitlana
AU - Tripsianes, Konstantinos
AU - Kateb, Fatiha
AU - Grummt, Ingrid
AU - Sattler, Michael
N1 - Publisher Copyright:
© 2015 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2015/4/3
Y1 - 2015/4/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84931287861&partnerID=8YFLogxK
U2 - 10.1093/nar/gkv365
DO - 10.1093/nar/gkv365
M3 - Article
C2 - 25916849
AN - SCOPUS:84931287861
SN - 0305-1048
VL - 43
SP - 5208
EP - 5220
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 10
ER -