1 346

Cited 12 times in

Function of multiple Lis-Homology domain/WD-40 repeat-containing proteins in feed-forward transcriptional repression by silencing mediator for retinoic and thyroid receptor/nuclear receptor corepressor complexes

Authors
 Hyo-Kyoung Choi  ;  Kyung-Chul Choi  ;  Hee-Bum Kang  ;  Han-Cheon Kim  ;  Yoo-Hyun Lee  ;  Seungjoo Haam, Hyoung-Gi Park  ;  Ho-Geun Yoon 
Citation
 MOLECULAR ENDOCRINOLOGY , Vol.22(5) : 1093-1104, 2008 
Journal Title
 MOLECULAR ENDOCRINOLOGY 
ISSN
 0888-8809 
Issue Date
2008
MeSH
Amino Acid Motifs/genetics ; Amino Acid Sequence ; Binding Sites/genetics ; Blotting, Western ; Cell Line ; Chromatin/metabolism ; Chromatin Immunoprecipitation ; DNA Mutational Analysis ; HeLa Cells ; Histones/metabolism ; Humans ; Immunoprecipitation ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism* ; Nuclear Receptor Co-Repressor 1 ; Protein Binding ; Receptors, Retinoic Acid/genetics ; Receptors, Retinoic Acid/metabolism* ; Receptors, Thyroid Hormone/genetics ; Receptors, Thyroid Hormone/metabolism* ; Repetitive Sequences, Amino Acid/genetics ; Repressor Proteins/genetics ; Repressor Proteins/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Transcription, Genetic*
Keywords
Amino Acid Motifs/genetics ; Amino Acid Sequence ; Binding Sites/genetics ; Blotting, Western ; Cell Line ; Chromatin/metabolism ; Chromatin Immunoprecipitation ; DNA Mutational Analysis ; HeLa Cells ; Histones/metabolism ; Humans ; Immunoprecipitation ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism* ; Nuclear Receptor Co-Repressor 1 ; Protein Binding ; Receptors, Retinoic Acid/genetics ; Receptors, Retinoic Acid/metabolism* ; Receptors, Thyroid Hormone/genetics ; Receptors, Thyroid Hormone/metabolism* ; Repetitive Sequences, Amino Acid/genetics ; Repressor Proteins/genetics ; Repressor Proteins/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Transcription, Genetic*
Abstract
Lis-homology (LisH) motifs are involved in protein dimerization, and the discovery of the conserved N-terminal LisH domain in transducin beta-like protein 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 oligomers in solution and that oligomerization depends on the presence of the LisH domain in each protein. Repression of transcription, as assayed using Gal4 fusion proteins, also depended on the presence of the LisH domain, 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 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. Finally, we observed that the WD-40 proteins RbAp46 and RbAp48 of the sin3A corepressor complex failed to dimerize. We also found the specific interaction UbcH/E2 with TBL1, but not RbAp46/48. Altogether, our results thus indicate that the presence of multiple LisH/WD-40 repeat containing proteins is exclusive to nuclear receptor corepressor/ silencing mediator for retinoic and thyroid receptor complexes compared with other class 1 histone deacetylase-containing corepessor complexes
Full Text
http://press.endocrine.org/doi/abs/10.1210/me.2007-0396
DOI
10.1210/me.2007-0396
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hee Bum(강희범)
Kim, Han Cheon(김한천)
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Lee, Yoo Hyun(이유현)
Choi, Kyung Chul(최경철)
Choi, Hyo Kyoung(최효경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106896
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links