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Vol. 14, No. 21, pp. 2737-2744, November 1, 2000
1 Department of Biochemistry and Molecular Biology,
University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA; 2 Division of Molecular Biology and Genetics, Department
of Oncological Sciences, University of Utah Health Science Center,
Salt Lake City, Utah 84132, USA
Ssn6-Tup1 regulates multiple genes in yeast, providing a paradigm
for corepressor functions. Tup1 interacts directly with histones H3 and
H4, and mutation of these histones synergistically compromises
Ssn6-Tup1-mediated repression. In vitro, Tup1 interacts preferentially
with underacetylated isoforms of H3 and H4, suggesting that histone
acetylation may modulate Tup1 functions in vivo. Here we report that
histone hyperacetylation caused by combined mutations in genes encoding
the histone deacetylases (HDACs) Rpd3, Hos1, and Hos2 abolishes
Ssn6-Tup1 repression. Unlike HDAC mutations that do not affect
repression, this combination of mutations causes concomitant
hyperacetylation of both H3 and H4. Strikingly, two of these class I
HDACs interact physically with Ssn6-Tup1. These findings suggest that
Ssn6-Tup1 actively recruits deacetylase activities to deacetylate
adjacent nucleosomes and promote Tup1-histone interactions.
[Key Words: Chromatin; transcription; nucleosome; yeast; acetylation]
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