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- Title
Function of multiple LisH/WD-40 repeat-containing proteins in feed-forward transcriptional repression by SMRT/N-CoR corepressor complexes.
- Authors
Choi, Hyo Kyoung; Choi, Kyung Chul; Kang, Hee Bum; Lee, Yoo-Hyun; Yoo, Jung-Yoon; Song, In-Jeong; Yoon, Ho-Geun
- Abstract
Lis-homology (LisH) motifs are involved in protein dimerization, and the discovery of the conserved N-terminal LisH domain in Transducin beta-like protien 1 and its receptor (TBL1 and TBLR1) led us to examine the role of this domain in transcriptional repression. Here we show that multiple beta-transducin (WD-40) repeat containing proteins interact to form a oligomers in solution and that oligomerization and Repression of transcription depends on the presence of the LisH domain in each protein, suggesting that oligomerization is a prerequisite for efficient transcriptional repression. Furthermore, we show that the LisH domain is responsible for the binding to the hypoacetylated histone H4 tail and for stable chromatin targeting by the nuclear receptor corepressor (N-CoR) complex. Mutations in conserved residues in the LisH motif of TBL1 and TBLR1 block histone binding, oligomerization, and transcriptional repression, supporting the functional importance of the LisH motif in transcriptional repression. Our results indicate that another WD-40 protein, TBL3, also preferentially binds to the N-terminal domain of TBL1 and TBLR1, and forms oligomers with other WD-40 proteins. In contrast, the WD-40 proteins RbAp46 and RbAp48 of the sin3A corepressor complex failed to dimerize. Our data support the hypothesis that the presence of multiple LisH/WD-40 repeat containing proteins is exclusive to N-CoR/SMRT complexes compared to other class 1 histone deacetylase-containing corepessor complexes. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea gorvenment (MOST) (No. R13-2002-054-04002-0) & (KOSEF 2007-8-1158)
- Publication
FASEB Journal, 2008, Vol 22, p200
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.22.2_supplement.200