title: Metabolic stress regulates basic transcription through acetyl-coenzyme A.
abstract: The acetylation and auto-acetylation of general transcription factors has recently been demonstrated, but the functional significance of these modifications is unclear. The presence of acetyl-coenzyme A activates basal transcription, and acetylation of transcription factor IIB (TFIIB) has been shown to activate transcription in several contexts. If auto-acetylation is an important pathway in eukaryotes, the regulatory pathways for acetyl-coenzyme A should be important in transcription regulation. Fasting represents an acute metabolic stress which should elevate levels of acetyl-coenzyme A, while mitochondrial aging represents a cumulative stress. We show that tissue-specific levels of acetylated TFIIB change dramatically in response to fasting in mice, suggesting a role for metabolism in the direct regulation of transcription. We also observed a large increase in acetyl-TFIIB in tissues from aged mice relative to younger mice. Sir2 family deacetylases, which regulate acetyl-coenzyme A synthesis, have recently been shown to impart longevity in a variety of organisms through a pathway related to calorie restriction. We hypothesize that protein acetylation and Sir2-related deacetylation may be tied to the metabolic regulation of transcription through the availability and action of acetyl-coenzyme A on key transcription factors and transcriptional regulators.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Choi
authors.forename: A
authors.initials: A
authors.lastname: Zimon
authors.forename: A
authors.initials: A
authors.lastname: Usheva
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000107:Acetylation; D000375:Aging / Q000502:physiology; D000818:Animals; D031204:Caloric Restriction; D005786:Gene Expression Regulation; D051379:Mice; D035581:Transcription Factor TFIIB / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D035581:Transcription Factor TFIIB; D000105:Acetyl Coenzyme A