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Molecular and Cellular Biology, January 2005, p. 324-335, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.324-335.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Reading and Function of a Histone Code Involved in Targeting Corepressor Complexes for Repression

Ho-Geun Yoon,1 Youngsok Choi,1 Philip A. Cole,2 and Jiemin Wong1*

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas,1 Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland2

Received 10 July 2004/ Returned for modification 11 August 2004/ Accepted 28 September 2004

A central question in histone code theory is how various codes are recognized and utilized in vivo. Here we show that TBL1 and TBLR1, two WD-40 repeat proteins in the corepressor SMRT/N-CoR complexes, are functionally redundant and essential for transcriptional repression by unliganded thyroid hormone receptors (TR) but not essential for transcriptional activation by liganded TR. TBL1 and TBLR1 bind preferentially to hypoacetylated histones H2B and H4 in vitro and have a critical role in targeting the corepressor complexes to chromatin in vivo. We show that targeting SMRT/N-CoR complexes to the deiodinase 1 gene (D1) requires at least two interactions, one between unliganded TR and SMRT/N-CoR and the other between TBL1/TBLR1 and hypoacetylated histones. Neither interaction alone is sufficient for the stable association of the corepressor complexes with the D1 promoter. Our data support a feed-forward working model in which deacetylation exerted by initial unstable recruitment of SMRT/N-CoR complexes via their interaction with unliganded TR generates a histone code that serves to stabilize their own recruitment. Similarly, we find that targeting of the Sin3 complex to pericentric heterochromatin may also follow this model. Our studies provide an in vivo example that a histone code is not read independently but is recognized in the context of other interactions.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6291. Fax: (713) 790-1275. E-mail: jwong{at}bcm.tmc.edu.

Molecular and Cellular Biology, January 2005, p. 324-335, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.324-335.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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