Introduction
The purpose of this site is to provide verified protocols for biology research.
As post-doctoral scholars/junior principle investigators, we have been looking for protocols that we can account for every day. Here, we put all the reliable protocols/reagents we have tested in this site. Unlike those methods described in scientific publications, our methods include great details and useful comments.
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Metabolic enzyme links glucose to gene expression
Nutrient availability and metabolism have long been thought to be a major reason affecting cellular energy homeostasis. The underlying mechanisms include changes of metabolic enzymes, fluctuations of intermediate metabolites and alteration of signaling pathways. In a recent issue of Science, a novel link has been revealed between glucose and changes of gobal gene expression.
Histone acetylation is a major form of chromatin remodeling which affects gene expression under various circumstances. A family of histone acetyltransferase utilizes acetyl CoA as sunstrate and modifies histones. The availability of acetyl CoA is determined by at least two enzymes, acetyl CoA synthase (ACS) from acetate and adenosine triphosphate-citrate lyase (ACL) from citrate. Using microscopic and biochemical approaches, Wellen et al found ACL is localized in cytoplasm and also nucleus. Knockdown of ACL greatly affects global histone acetylation while decrease of ACS has little impact. Interestingly, the changes of acetylation is limited to histones since cytoplasmic targets are not affected including p53 and tubulin. Histone acetylation increases substantially during cell proliferation. Wellen and colleagues demonstrate that ACL is the major player involved in the histone acetylation when cells grow in the presence of growth factors. Glucose deprivation significantly decreases histone modification even in the presence of ACL since glucose is the major source of citrate, the substrate to generate acetyl CoA. Similarly, histone acetylation in 3T3-L1 adipocyte differentiation is also dependent on ACL and availability of glucose.
The elucidation of glucose and acetylation connection provides a novel link between extracelluar nutrients and intracellular signal transduction pathway. However, more work may be required to examine the specificity of histone modifications by glucose-ACL pathway udner different conditions such as cancer, obesity and diabetes. ...
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