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.

Molecular Endocrinology
Hyo-Kyoung ChoiHo-Geun Yoon

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 othe...Continue Reading

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Citations

Jan 18, 2011·Nature Structural & Molecular Biology·Jasmeen OberoiJohn W R Schwabe
Dec 21, 2011·Molecular and Cellular Biology·Kyunghwan KimWoojin An
Jul 1, 2017·Open Biology·Louisa M SalemiCaroline Schild-Poulter
Jul 3, 2017·BMC Cancer·Louisa M SalemiCaroline Schild-Poulter
Jul 23, 2015·Analytical Cellular Pathology (Amsterdam)·Stefano GuarinielloSusan Costantini
Aug 21, 2021·Frontiers in Cell and Developmental Biology·Nicole A LynnJorge Z Torres
Jul 23, 2011·Molecular Cell·Hyo-Kyoung ChoiHo-Geun Yoon

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