Regulation of histone modification state by the anaphase promoting
complex.
Vijay Ramaswamy, Jessica Uhren, Karen Robinson,
Richelle Sopko, Michael Schultz
Biochemistry, University of Alberta,
MSB 5-73, Edmonton, AB T6G 2H7, Canada
Post-translational
modification of histones plays a key role in transcriptional regulation.
Because histone-directed enzymes act at specific promoters and often
more extensively throughout the genome, global changes in histone
modification states can accompany large-scale transcriptional
reprogramming events in metazoans. Widespread effects on gene expression
also characterize the developmental program executed by budding yeast in
response to nutrient limitation. Here we show that normally Ser 10
dephosphorylation of histone H3 and deacetylation of H2B, H3 and H4 is
associated with genomewide reprogramming of transcription in cells
challenged by nutrient withdrawal. These global changes in the
chromosomal landscape during entry into quiescence are dependent on the
anaphase promoting complex (APC), a conserved multi-subunit ubiquitin
ligase (E3) previously characterized as a cell cycle regulator of the
physical state of the chromosomes. When APC function is compromised by
either APC10 null or conditional APC11 mutations, the post-translational
modification of histones during entry into G0 is misregulated on a
global scale. Furthermore, these perturbations in histone modification
state are accompanied by widespread changes in transcriptional events.
Our results place the APC in a regulatory pathway that governs global
changes in the covalent modification state of the chromosomes during a
physiological response involving large scale transcriptional
reprogramming.
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