Home

About

Advanced Search

Browse by Discipline

Scientific Societies

E-print Alerts

Add E-prints

E-print Network
FAQHELPSITE MAPCONTACT US


  Advanced Search  

 
MOLECULAR AND CELLULAR BIOLOGY, 0270-7306/00/$04.00 0
 

Summary: MOLECULAR AND CELLULAR BIOLOGY,
0270-7306/00/$04.00 0
Sept. 2000, p. 6882­6890 Vol. 20, No. 18
Copyright © 2000, American Society for Microbiology. All Rights Reserved.
-Catenin­Histone Deacetylase Interactions Regulate the
Transition of LEF1 from a Transcriptional Repressor to
an Activator
ANDREW N. BILLIN, HILARY THIRLWELL, AND DONALD E. AYER*
Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550
Received 26 May 2000/Accepted 19 June 2000
Recent evidence suggests that certain LEF/TCF family members act as repressors in the absence of Wnt
signaling. We show here that repression by LEF1 requires histone deacetylase (HDAC) activity. Further, LEF1
associates in vivo with HDAC1, and transcription of a model LEF1-dependent target gene is modulated by the
ratio of HDAC1 to -catenin, implying that repression by LEF1 is mediated by promoter-targeted HDAC.
Consistent with this hypothesis, under repression conditions the promoter region of a LEF1 target gene is
hypoacetylated. By contrast, when the reporter is activated, its promoter becomes hyperacetylated. Coexpres-
sion of -catenin with LEF1 and HDAC1 results in the formation of a -catenin/HDAC1 complex. Surprisingly,
the enzymatic activity of HDAC1 associated with -catenin is attenuated. Together, these findings imply that
activation of LEF1-dependent genes by -catenin involves a two-step mechanism. First, HDAC1 is dissociated
from LEF1 and its enzymatic activity is attenuated. This first step yields a promoter that is inactive but poised

  

Source: Ayer, Don - Huntsman Cancer Institute, University of Utah

 

Collections: Biology and Medicine