Event Title
Set3C Stimulates NuA4 Interaction with Nucleosomes and Occupancy Transcribed Genes
Faculty Mentor
Daniel Ginsburg
Major/Area of Research
Biomedical Sciences
Description
Gene expression in eukaryotic cells is regulated in large part by chromatin.
For efficient transcription to take place, chromatin must be disassembled.
A critical step in chromatin disassembly is histone acetylation, which is
regulated by the opposing activities of lysine acetyltransferase (KAT) and
histone deacetylase (HDA) complexes. The NuA4 KAT has been shown to
preferentially bind nucleosomes methylated on histone H3 lysines 4 and
36 (H3K4/36me). Nucleosome binding of the Rpd3C(S) and SET3C HDACs is
stimulated by H3K36me and H3K4me respectively. Because they have been
shown to bind the same histone methylation marks, we wanted to test the
hypothesis that one mechanism for the regulation of nucleosome acetylation
is through competition between NuA4 and the Rpd3C(S) and SET3C
HDACs for nucleosome binding. We analyzed phenotypes, H4 acetylation,
NuA4-nucleosome interactions, and NuA4 occupancy at transcribed genes
in mutations that affected Rpd3C(S) and SET3C complex integrity (rco1_ and
set3_ respectively), SET3C deacetylase activity (hos2_), and H3K4 methylation
(set1_). We expected that loss of Rpd3C(S) or SET3C chromatin binding,
but not deacetylase activity would lead to increased NuA4-nucleosome
interactions, more NuA4 occupancy at transcribed genes, and elevated H4
acetylation. Surprisingly, our results suggested that Rpd3C(S) and SET3C
stimulate NuA4 interaction with nucleosomes and occupancy at transcribed
genes. Loss of SET1 did not suppress the phenotypes or significantly reduce
the elevated H4 acetylation in set3_ cells. Together, these results support a
model in which both Rpd3C(S) and SET3C stimulate NuA4 interaction with
nucleosomes and recruitment to transcribed genes.
Set3C Stimulates NuA4 Interaction with Nucleosomes and Occupancy Transcribed Genes
Gene expression in eukaryotic cells is regulated in large part by chromatin.
For efficient transcription to take place, chromatin must be disassembled.
A critical step in chromatin disassembly is histone acetylation, which is
regulated by the opposing activities of lysine acetyltransferase (KAT) and
histone deacetylase (HDA) complexes. The NuA4 KAT has been shown to
preferentially bind nucleosomes methylated on histone H3 lysines 4 and
36 (H3K4/36me). Nucleosome binding of the Rpd3C(S) and SET3C HDACs is
stimulated by H3K36me and H3K4me respectively. Because they have been
shown to bind the same histone methylation marks, we wanted to test the
hypothesis that one mechanism for the regulation of nucleosome acetylation
is through competition between NuA4 and the Rpd3C(S) and SET3C
HDACs for nucleosome binding. We analyzed phenotypes, H4 acetylation,
NuA4-nucleosome interactions, and NuA4 occupancy at transcribed genes
in mutations that affected Rpd3C(S) and SET3C complex integrity (rco1_ and
set3_ respectively), SET3C deacetylase activity (hos2_), and H3K4 methylation
(set1_). We expected that loss of Rpd3C(S) or SET3C chromatin binding,
but not deacetylase activity would lead to increased NuA4-nucleosome
interactions, more NuA4 occupancy at transcribed genes, and elevated H4
acetylation. Surprisingly, our results suggested that Rpd3C(S) and SET3C
stimulate NuA4 interaction with nucleosomes and occupancy at transcribed
genes. Loss of SET1 did not suppress the phenotypes or significantly reduce
the elevated H4 acetylation in set3_ cells. Together, these results support a
model in which both Rpd3C(S) and SET3C stimulate NuA4 interaction with
nucleosomes and recruitment to transcribed genes.