Glucose regulation of histone acetylation in yeast and mammalian
cells.
Amber Mosley, Sabire Ozcan
Department of Biochemistry, University of Kentucky, 800 Rose St MN663,
Lexington, KY 40517, USA (almosl2@uky.edu)
Glucose is the preferred carbon source for all organisms. For this
reason various signaling pathways have been devised for cells to sense
glucose and then transmit a signal to stimulate glucose uptake and
metabolism. In many organisms, including yeast and mammals, the end
result of these elaborate signaling pathways is an up-regulation of
transcription leading to glucose induction of genes involved in glucose
metabolism. In yeast, the target of the glucose signal is the
transcription factor Rgt1. In response to glucose, Rgt1 is modified
which stimulates its conversion from a repressor to an activator.
Regulation of HXT gene expression also requires modulations in local
histone structure which are mediated by Rgt1. A number of other proteins
also play a role in the regulation of histone acetylation including
Mth1, Ssn6, and Tup1. These proteins are also required for proper
regulation of HXT gene expression through Rgt1. In mammals, the
pancreatic beta cells are responsible for the production of insulin,
which is required to stimulate glucose uptake into fat and muscle cells.
In beta-cells, glucose stimulates an up-regulation of insulin gene
transcription which is mediated by the transcription factor Pdx-1. Like
Rgt1, Pdx-1 is required for the regulation of histone acetylation at the
insulin promoter. Our hypothesis is that Rgt1 may also play a role in
the regulation of histone modification through the recruitment of
various co-regulatory proteins such as Ssn6/Tup1.