Acetyl-CoA induces transcription of the key G1 cyclin CLN3 to promote entry into the cell division cycle in Saccharomyces cerevisiae
Lei Shi,Benjamin P. Tu +1 more
TLDR
It is shown that a central metabolite of glucose catabolism, acetyl-CoA, induces CLN3 transcription by promoting the acetylation of histones present in its regulatory region.Abstract:
In budding yeast cells, nutrient repletion induces rapid exit from quiescence and entry into a round of growth and division. The G1 cyclin CLN3 is one of the earliest genes activated in response to nutrient repletion. Subsequent to its activation, hundreds of cell-cycle genes can then be expressed, including the cyclins CLN1/2 and CLB5/6. Although much is known regarding how CLN3 functions to activate downstream targets, the mechanism through which nutrients activate CLN3 transcription in the first place remains poorly understood. Here we show that a central metabolite of glucose catabolism, acetyl-CoA, induces CLN3 transcription by promoting the acetylation of histones present in its regulatory region. Increased rates of acetyl-CoA synthesis enable the Gcn5p-containing Spt-Ada-Gcn5-acetyltransferase transcriptional coactivator complex to catalyze histone acetylation at the CLN3 locus alongside ribosomal and other growth genes to promote entry into the cell division cycle.read more
Citations
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The Emerging Hallmarks of Cancer Metabolism
TL;DR: This Perspective has organized known cancer-associated metabolic changes into six hallmarks: deregulated uptake of glucose and amino acids, use of opportunistic modes of nutrient acquisition, useof glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, increased demand for nitrogen, alterations in metabolite-driven gene regulation, and metabolic interactions with the microenvironment.
Journal ArticleDOI
Acetyl Coenzyme A: A Central Metabolite and Second Messenger
TL;DR: By influencing the acetylation profile of several proteins, including histones, acetyl-CoA controls key cellular processes, including energy metabolism, mitosis, and autophagy, both directly and via the epigenetic regulation of gene expression.
Journal ArticleDOI
Acetyl-CoA and the regulation of metabolism: mechanisms and consequences
Lei Shi,Benjamin P. Tu +1 more
TL;DR: Understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes.
Journal ArticleDOI
Acetate dependence of tumors.
Sarah A. Comerford,Zhiguang Huang,Xinlin Du,Yun Wang,Ling Cai,Agnieszka K. Witkiewicz,Holly Walters,Mohammed N. Tantawy,Allie Fu,H. Charles Manning,Jay D. Horton,Robert E. Hammer,Steven L. McKnight,Benjamin P. Tu +13 more
TL;DR: It is shown that the nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl -CoA for tumors by capturing acetate as a carbon source.
Journal ArticleDOI
Akt-Dependent Metabolic Reprogramming Regulates Tumor Cell Histone Acetylation
Joyce V. Lee,Alessandro Carrer,Supriya Shah,Nathaniel W. Snyder,Shuanzeng Wei,Sriram Venneti,Andrew J. Worth,Zuo-Fei Yuan,Hee-Woong Lim,Shichong Liu,Ellen Jackson,Nicole M. Aiello,Naomi B. Haas,Timothy R. Rebbeck,Alexander R. Judkins,Kyoung-Jae Won,Lewis A. Chodosh,Benjamin A. Garcia,Ben Z. Stanger,Michael Feldman,Ian A. Blair,Kathryn E. Wellen +21 more
TL;DR: It is demonstrated that acetyl-CoA is dynamically regulated by glucose availability in cancer cells and that the ratio of acetyl -CoA:coenzyme A within the nucleus modulates global histone acetylation levels.
References
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Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex.
Patrick A. Grant,Laura J. Duggan,Jacques Côté,S M Roberts,James E. Brownell,Reyes Candau,Reiko Ohba,Tom Owen-Hughes,C D Allis,Fred Winston,Shelley L. Berger,Jerry L. Workman +11 more
TL;DR: The function of Gcn5 as a hist one acetyltransferase within the Ada and SAGA adaptor complexes indicates the importance of histone acetylation during steps in transcription activation mediated by interactions with transcription activators and general transcription factors.