Gene Regulation - GRE Subject Test: Biochemistry, Cell, and Molecular Biology

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Question

Histone acetyltransferases (HATs) transfer acetyl groups from acetyl CoA to lysine residues on histones. What is the purpose of this transfer?

Answer

The correct answer is to promote formation of euchromatin and increase gene expression. Acetylation of histones "relaxes" DNA coiling around histones by reducing the affinity between histones and DNA. This allows transcription factors to bind promoter regions and promote increased gene expression via transcription.

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Question

What is the role of mediator in gene expression?

Answer

The correct answer is that mediator is a coactivator of transcription and serves to recruit transcription factors and RNA polymerase II. Mediator does not directly initiate transcription; however, by protein-protein interactions, it recruits the necessary proteins to sites of transcription.

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Question

NFkB is a transcription factor that is held inactive in the cytoplasm when bound by its inhibitor, IkB. Upstream signaling that activates NFkB causes what effect?

Answer

Upstream signaling, such as from a toll-like receptor, causes IKK to phosphorylate IkB, signaling for its ubiquitin-mediated degradation. Since NFkB is no longer bound by its inhibitor, IkB, it translocates to the nucleus where it binds specific motifs in the genome to recruit other transcriptional machinery and initiate transcription.

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Question

Which of the following is not a way in which transcription factors influence gene-specific transcription?

Answer

The correct answer is recruiting DNA polymerase. DNA polymerase is involved in DNA replication, not transcription. Pioneer transcription factors can bind specific DNA motifs and promote euchromatin formation, allowing other transcription factors to bind the less organized DNA. Transcription factors can recruit other transcription factors and the RNA polymerase holoenzyme to promoters to promote gene-specific transcription.

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Question

In regards to the lac operon in the presence of lactose, will the genes be transcribed in large amounts?

Answer

Activation of the lac operon is necessary for the transport and metabolism of lactose sugars by E. coli. Lactose sugars actively work to remove a repressor that statically inhibits transcription; however, high concentrations of glucose (and, thus, low concentrations of cAMP) will prevent these genes from being transcribed rigorously. In order for the lac operon to be active at high levels, lactose must be present and glucose must be absent.

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Question

Which of the following conditions are crucial to maintain high activation of the lac operon?

Answer

The lac operon is a system designed to only express particular proteins when the concentration of glucose is low and the concentration of lactose is high. The common cellular response to a low concentration of glucose is to increase the concentration of cAMP in order to activate various alternative metabolic pathways. Both a high concentration of cAMP and a high concentration of lactose are necessary to get sustained expression of the lac operon. When glucose levels begin to rise, the cAMP concentration will begin to fall and the operon function will deteriorate.

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Question

Which of the following choices best represents the phenotype of a cell containing a mutation in the lac I gene?

Answer

lac I is the gene that encodes for the repressor of the lac operon. If there is no repressor, the cell will constantly express the genes present in the lac operon whether or not the typical conditions are present.

A mutation of the gene encoding -galactosidase permease (lac Y) would prevent lactose from entering the cell. A mutation in the gene encoding -galactosidase (lac Z) would prevent the breakdown of lactose. A mutation in the promoter region would prevent RNA polymerase from binding.

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Question

In prokaryotes, functionally related genes are sometimes position adjacent to each other in the genome and can under the control of the same regulatory machinery. What are these called?

Answer

Prokaryotic organisms often have functionally related genes joined together on the chromosome under the direction of a single promoter. These structures are called operons. Operons have additional sequences, called operators that can be bound by either repressor or activator proteins, which will repress or activate transcription of the operon. One commonly studied example is the lac operon, whose genes encodes products required for lactose metabolism.

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Question

Inducible operons are bound by a repressor and turned off under normal conditions. How are these operons turned on?

Answer

Negatively regulated operons that are said to be inducible have their operator sequence bound by a repressor molecule normally. That leads to these operons being off normally. For these operons to be turned on and transcribed, a small molecule called an inducer has to bind to and inactivate the repressor protein.

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Question

Mutations in two or more genes cause cell death, however, a mutation in only one of the genes is not lethal.

Which of the following best describes this phenomenon?

Answer

Synthetic lethality is the correct answer. The combinatorial effect of multiple mutated genes disrupts homeostasis in cells, inducing cell death. A mutation in only one gene can be compensated for in cells by altering the expression of other genes, such as turning on anti-apoptotic signaling pathways.

Oncogene addiction occurs when a tumor cell relies on the expression of a particular oncogene (mutated gene) for survival.

Oncogenic shock refers to an increase in pro-apoptotic signaling and a decrease in anti-apoptotic signaling upon removal of an oncoprotein.

Apoptosis refers to the process of programmed cell death.

Secondary mutations occur in a cancer cell that is treated with a therapeutic agent to promote resistance to that specific agent.

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Question

When modifiying histones with either activating or repressing marks, such as with acetyl and methyl groups, histone acetyltransferases and histone methyltransferases normally modify which amino acid?

Answer

Histones are almost always modified on lysines. Acetylation normally is an activating mark, and methylation is normally a repressing mark of chromatin structure.

Note that guanine is not an amino acid, but a nucleotide.

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Question

Which of the following is indicative of enhancers in the chromatin landscape of a given cell?

Answer

The correct answer is all of the other answers are correct. H3K4me1 (Histone 3 Lysine 4 methyl 1) marks where enhancers are in the chromatin landscape. By further identifying H3K27Ac or H3K27Me3 marks on the same histone, we can determine whether the enhancer is active or inactive, respectively. A DNase 1 hypersensitivity assay will preferentially cut open chromatin, which often is indicative of enhancer regions in the chromatin landscape.

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Question

Where are promoters typically found in DNA?

Answer

Promoters are the sites where transcription factors and RNA polymerase bind to initiate transcription. It makes sense that the promoter would be found upstream of a gene (i.e. before a gene). "Downstream of the coding region" and "in the middle of the coding region" are redundant answers, and neither describes a location where a promoter would normally be located. The 3' UTR describes a region of mRNA and, thus, has nothing to do with promoters.

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Question

__________ are regions of DNA, located __________ of a gene, that will increase its expression.

Answer

As the name suggests, enhancers enhance the expression of a gene; they increase the number of mRNA transcripts produced from said gene. Silencers do the opposite, and repress the expression of a gene by serving as a binding site for repressors. It does not matter exactly how far enhancers are from the gene (either upstream or downstream) as long as they are geometrically close.

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Question

Which of the following does not represent a feature of bacterial transcription that is not found in eukaryotic transcription?

Answer

Bacterial RNA polymerase is very similar to eukaryotic RNA Polymerase II in that both have many subunits and form a holoenzyme with cofactors. The rest of the answers are in fact unique to bacterial transcription.

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Question

What proteins enhance transcription by promoting the recruitment of transcription factors and stabilizing the RNA polymerase holoenzyme at the promoter?

Answer

Coactivators increase gene expression by binding to a transcription factor, recruiting other transcription factors and cofactors, and stabilizing the RNA polymerase holoenzyme to ensure that it can pass the promoter and begin transcribing coding sequence. Corepressors repress transcription, while histone methyl/acetlytransferases act on histone proteins. DNA methyltransferases methylate DNA to establish epigenetic marks that generally inhibit transcription.

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Question

What regulatory element promotes RNA polymerase II binding as well as binding of factors that facilitate the unwinding of DNA prior to translation?

Answer

The correct answer is TATA box. Found in about 24% of human gene promoters, this regulatory element is mostly found in genes transcribed by RNA polymerase II, and as such, recruits this enzyme to the promoter. Additionally, the TATA binding protein aids in unwinding DNA.

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Question

In a hypothetical situation, the enhancer region of gene X, which controls tail length in mice, is mutated such that transcription factors bind to the enhancer region at a much higher efficiency than if the region were wild-type. What is a reasonable phenotypic outcome possible from this mutation in gene X's enhancer region?

Answer

This question is inspired by a real life example, in which if you put a bat enhancer region in front of the gene that controls limb development in mice, the limbs are longer due to changes in the enhancer activity, which increases the activity of the promoter. By permitting more transcription factor interaction with the regulatory region, one might expect that this type of mutation may increase the tail length of the mouse because more "pro-tail length" protein is being made.

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Question

Which of the following types of RNA have been shown to regulate protein synthesis?

I. lncRNA

II. miRNA

III. tRNA

Answer

Protein synthesis can be directly affected by molecules involved in translation, or indirectly by molecules involved in the transcription of mRNA templates.

Transfer RNA (tRNA) is involved in translation and serves the function of bringing amino acids to ribosomes. Due to its important function in translation tRNA, is capable of globally controlling translation and, therefore, is involved in protein regulation.

Long non-coding RNA (lncRNA) has been shown to regulate transcription in a number of ways. One of the most prominent is the existence of a lncRNA (Xist) that inactivates the majority of the extra X-chromosome in human females.

Micro RNA (miRNA) is involved in a process known as RNAi and is capable of controlling the translation of targeted molecules of mRNA.

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Question

X-chromosome inactivation occurs in females in which one X-chromosome is silenced and transcriptionally inactivated. The X-inactive specific transcript (Xist) gene is responsible for mediating this inactivation.

What does Xist encode?

Answer

The correct answer is long non-coding (lnc) RNA. Xist lncRNA coats the X-chromosome from which it is transcribed, effectively silencing that X-chromosome. MicroRNAs are small RNAs (~20 base pairs (bp)) and play a role in RNA silencing and post-transcriptional regulation of gene expression. Short interfering RNAs are double-stranded (20-25 bp) and play a role in post-transcriptional gene silencing. Piwi-interacting RNAs are small non-coding RNAs that interact with piwi proteins in epigenetic and post-transcriptional silencing of genetic elements such as retroposons. While MicroRNAs, siRNAs and Piwi-interacting RNAs all silence genes, the mechanism of X-chromosome inactivation requires Xist lncRNA.

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