Repression of the HO gene by the alpha2 and a1 homeodomain
proteins.
Jonathan Mathias, Andrew Vershon
Waksman
Institute, Rutgers University, 190 Frelinghuysen Rd, Piscataway, NJ
08854, USA
The homeodomain is a highly conserved DNA-binding motif
found in transcriptional regulators from yeast to humans. The yeast
MATalpha2 and MATa1 homeodomain proteins form a heterodimer
(alpha2/a1) that binds DNA upstream of several haploid-specific
genes to repress their transcription in the diploid cell type. One such
gene is HO, which encodes a protein that initiates mating type
switching in haploid yeast. Expression of HO is regulated by an
extensive promoter that resembles promoters found in higher-ordered
eukaryotes, and alpha2/a1 represses HO transcription by
binding to ten sites within this promoter. We show that alpha2/a1
binds to these individual sites with differing affinity, and potentially
regulates HO through cooperative interactions between
alpha2/a1 heterodimers bound to strong and weak-affinity sites.
The alpha2/a1 complex represses target genes through interactions
with the Tup1/Ssn6 corepressor, which interacts with subunits of the
Srb/Mediator complex as well as several histone deacetylases. We will
report on the progress of determining the factors that repress HO
in diploid yeast in conjunction with alpha2/a1 and Tup1/Ssn6, and
whether these repressor proteins prevent DNA-binding and transcription
regulation by Swi5/Pho2 and other HO activators. These and other
experiments will determine whether alpha2/a1 acts in a local
manner around each individual binding site, or if a repressive chromatin
environment is set up across the promoter.
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