In addition to being metabolized for energy, the ketone body β-hydroxybutyrate (BHB) can also react with lysine residues of histone proteins.Which statement best explains the general upregulation of gene expression following histone β-hydroxybutyrylation?  β-Hydroxybutyrylation:A.decreases the binding interaction between histones and the DNA backbone.B.increases the binding interaction between histones and the nitrogenous bases of DNA.C.increases the binding interaction between histones and the RNA backbone.D.decreases the binding interaction between histones and the nitrogenous bases of RNA.

Although the ketone body β-hydroxybutyrate (BHB) is commonly associated with the pathologic condition diabetic ketoacidosis, its most recognized physiologic function is as an alternative fuel source produced by the liver when glucose is sparse.  More recently, evidence has emerged that BHB also serves as a signaling and regulatory molecule that is associated with protection against the effects of aging, inflammation, and neuronal excitotoxicity.BHB released from the liver is taken up by muscle, brain, and other peripheral tissues, where it is trafficked to the mitochondria.  BHB is reversibly converted to acetoacetyl-CoA (Figure 1), which can then be processed through β-oxidation.  Because BHB is processed in the mitochondria, the cytosolic NAD+ pool is preserved.  In addition to its use as a redox cofactor, cytosolic NAD+ also acts as a substrate for the sirtuin and poly(ADP-ribose) polymerase (PARP) enzymes; by preserving the cytosolic NAD+ pool, increased BHB levels enhance the anti-aging and anti-apoptotic effects of the sirtuin and PARP enzymes.Figure 1  Conversion of BHB to acetoacetyl-CoABHB acts directly as an agonist for several receptors, including the hydroxycarboxylic acid receptor 2 (HCAR2), a Gi-coupled G protein–coupled receptor (GPCR) that upon activation inhibits adenylyl cyclase and its downstream effectors.  In adipocytes, BHB-mediated activation of HCAR2 reduces lipolysis, decreasing serum levels of proinflammatory free fatty acids.  In the colonic epithelium, HCAR2 activation is critical in the maintenance of gut membrane integrity.  In this way, BHB acts similarly to the short-chain fatty acids (eg, butyric acid), produced from fermentation of dietary fiber, in protecting gut health.Several mechanisms have been proposed to explain BHB's action as a neuroprotectant against excitotoxicity.  In glutamatergic neurons, BHB inhibits vesicular glutamate transporter 2 (VGLUT2), inhibiting the packaging of the excitatory neurotransmitter glutamate.  In GABAergic neurons, BHB infusion stimulates production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and decreases α-ketoglutarate levels. Question 40Based on the passage, hepatocytes (ie, liver cells) that are producing BHB are also most likely to have:A.downregulated phosphofructokinase-2 (PFK2) activity.B.downregulated phosphorylase kinase activity.C.upregulated acetyl-CoA carboxylase (ACC) activity.D.upregulated glycogen synthase activity.

Increase in histone deacetylases.B. Increase in histone acetyltransferases.C. Decrease in DNA methyltransferases.D. Decrease in CpG methylation of promoter

Histone proteins can be modified through methlyation, acetylation, and phosphorylation. Most oftenit is lysine (K) amino acids that are modified. To investigate the role of the acetylation of a lysine atposition 56 (K56) in histone H3, a mutation was made where the lysine is replaced with an arginineresidue, which prevents acetylation. This mutation is lethal at the embryonic stage.a. What effect would this mutation have on the packing of chromatin? Explain your answer. (2marks)b. What could be the reason that this mutation is lethal? Suggest a reason and explain yourchoice. (3 marks)Questions continue over the page.

What is the effect of high levels of histone acetylation on the expression of a gene?Group of answer choicesThis changes the splicing of the geneIt causes the chromatin to condenseThe gene becomes expressed lessThe gene becomes expressed more

Which of the following is most likely to increase expression of a particular gene? Group of answer choicesa mutation in a silencerrecruitment of histone methyltransferasesrecruitment of histone deacetylasescis regulation by a lncRNA