Hauser Exam 3

Which of the following is NOT a main role for histone-modifying proteins?

"proofreaders" that confirm the DNA sequence is correct. Histone-modifying proteins can be "writers" that add chemical groups to histones, "readers" that interpret the modifications, and "erasers" that remove chemical groups.

Genomic imprinting

(1) Parent-of-Origin MAE: Imprinting in early embryonic cells results in some allele pairs showing expression of only the maternal or the paternal allele.

Inactivation of the X chromosome

(2) Random MAE: Inactivation of the X Chromosome in early embryonic cells will silence one X chromosome to compensate for the increased dosage of X-linked genes that mammalian females have compared to males.

Random MAE of autosomal genes

(3) Random MAE of Autosomal Genes where regulation in somatic progenitor cells results in random expression of neither allele, only maternal, only paternal, or both alleles (biallelic) in cells within a given tissue.

What is ubiquitin?

A small protein found in all eukaryotic cells that is involved in targeting proteins for degradation

Which of the following is NOT a function of long noncoding RNAs (lncRNAs)?

Act as converters that bind complex machinery to reverse transcribe RNA into DNA. Long noncoding RNAs (lncRNAs) can interact with selected regions of the genome by: (1) Acting as decoys that bind transcription factors and prevent transcription. (2) Serving as adapters that link two or more proteins together to form a functional complex. (3) Serving as guides that deliver chromatin modifying proteins to specific locations in the genome. (4) Binding to DNA regions upstream and downstream of genes to form enhancer-like loops.

In wild-type cultured cells, actin mRNA (a zip code containing mRNA) is localized to the cell periphery and only translated at the cell periphery. In an experiment, Src was knocked down with RNAi. What phenotype would you expect from this experiment?

Actin mRNA would localize to the cell periphery, but it would not be translated. Src is a kinase that acts to phosphorylate ZPB1 at the cell periphery.

Which of the following is an example of a manmade carcinogen?

Air pollution

Which of the following is not true of DNA methylation and cancer?

All regions of the genome of cancer cells are hypomethylated when compared to normal cells. Selective hypermethylation of promoter-associated CpG islands silences certain genes, including tumor-suppressor genes, often in a tumor-specific fashion. Hypomethylation of repetitive DNA sequences in heterochromatic regions increase chromosome rearrangements, changes in chromosome number, and lead to transcriptional activation of transposable DNA sequences.

__________________ is a mechanism that allows the proteome of an organism to exceed the number of genes in its genome.

Alternative splicing

Which of the following mechanisms is an example of posttranscriptional regulation?

Alternative splicing Other examples of posttranscriptional regulation include adding a 5' cap and 3' poly-A-tail to an mRNA, localization of mRNAs to specific regions of a cell, and stabilization or degradation of an mRNA.

In an acute transforming retrovirus, what is v-onc?

An oncogene acquired from the host that can transform other infected host cells. Retroviruses can pick up host genes in their genome during their lifecycles. If a retrovirus picks up a proto-oncogene that becomes mutated or overexpressed through insertion to become an oncogene, infection by the virus can transform host cells.

Which of the following classes of long noncoding RNAs (lncRNA) partially overlap protein-coding genes and are transcribed in the opposite direction of the protein-coding gene?

Antisense There are four types of long noncoding RNA (lncRNA): (1) Antisense lncRNA partially overlap protein-coding genes and are transcribed in the opposite direction of the protein-coding gene. (2) Intronic lncRNA genes are located within introns, and their transcription does not overlap with the adjacent exon. (3) Bidirectional lncRNA genes use the promoter of a protein-coding gene but are transcribed in the opposite direction. (4) Intergenic lncRNA genes are discrete transcription units located outside the protein-coding region.

Which of the following is not true of genomic imprinting?

Beckwith-Wiedemann (BWS) is typically due to a mutation in the DNA sequence of a gene. BWS is not caused by mutation in the DNA sequence of the gene, nor is it associated with any chromosomal aberrations. The genes associated with Beckwith-Wiedemann syndrome (BWS) are located in a cluster of epigenetically imprinted genes on the short arm of human chromosome 11.

role of epigenetics in behavior.

Behavior may be regulated by epigenetic mechanisms that operate in the different regions of the brain in mice to cause preferential expression of maternal or paternal alleles and imprint nearly 1,000 genes. Epigenetic changes have been documented during the progression of human neurodegenerative disorders and in neuropsychiatric diseases that show altered behavior phenotypes. High levels of glucocorticoid receptor (GR) gene promoter methylation were found in suicide victims with a history of child abuse, but not in suicide victims with no history of child abuse or in others who died suddenly of unrelated causes. Stress-induced epigenetic changes that occur prenatally or early in life can influence behavior.

How is translation activated on a translationally dormant CPE containing mRNA?

CPEB is phosphorylated by a kinase, which allows the poly-A tail of the mRNA to lengthen. The longer poly-A tail interacts with PABP, which stably interacts with eIF4G. eIF4G can now interact with eIF4E, an interaction that is required for translation initiation.

Which of the following is NOT true of epigenetic alterations in cancer?

Cancer results from the accumulation of either genetic or epigenetic changes, but not both. Cancer is now viewed as a disease that usually results from the accumulation of both genetic and epigenetic changes. Epigenetic mechanisms can silence individual tumor-suppressor genes. In fact, epigenetic modifications can silence multiple genes, making them more effective in transforming normal cells into malignant cells than sequential mutations of single genes.

Which of the following is NOT a true statement regarding DNA methylation?

CpG hypermethylation is associated with elevated levels of transcription. CpG hypomethylation, NOT hypermethylation, is associated with elevated levels of transcription and genes involved in tissue-specific functions. For example, in bone and joint cartilage, genes associated with skeletal and cartilage development are hypomethylated and transcriptionally active.

What is the first step in the degradation of most mRNAs?

Deadenylation After deadenylation, the mRNA is either degraded from 3'-5' by the exosome or decapped and then degraded 5'-3' by the exoribonuclease XRN1.

Which of the following is NOT true of random inactivation of the X chromosome?

Embryonic cells in female mammals always inactivate the maternal X chromosome. In female mammals, about half of embryonic cells randomly inactivate the maternal X chromosome and the other half inactive the paternal chromosome. Once inactivated, the same X chromosome remains silenced in all cells descended from this progenitor cell. Two long noncoding RNAs (lncRNAs) are important in this process: (1) Xist is expressed on the inactivated X chromosome, coats the entire chromosome, converting it to a Barr body, which is highly condensed and genetically silent chromatin structure. (2) Tsix is expressed on the active X chromosome and represses expression of the Xist lncRNA, thus preventing the active X chromosome from being silenced. previous

Most somatic cells in an adult organism are in what stage of the cell cycle?

G0 - metabolically active but no growth or division occurs.

Select the three statements that are typically true of genes in an "closed" configuration that cannot be transcribed.

Gene regions have a highly condensed chromatin structure. DNA is methylated at CpG islands. Histones are deacetylated.

Select the three statements that are typically true of genes in an "open" configuration that can be transcribed.

Gene regions have an uncondensed chromatin structure. DNA is unmethylated. Histones are acetylated.

Which of the following is NOT true of epigenetic changes in cells?

Imprinted genes escape the pattern of histone acetylation and deacetylation and show parent-specific patterns and activity of either the maternal or paternal allele. Imprinted genes show parent-specific patterns of methylation and activity of one allele because they escape the pattern of demethylation and remethylation, NOT histone acetylation and deacetylation.

The Philadelphia chromosome is a translocation between chromosomes 22 and 9 that leads to translation of a BCR-ABL fusion protein. The normal ABL gene is a proto-oncogene that codes for a kinase involved in a cell signaling pathway. How does this chromosome abnormality lead to cancer?

In the fusion protein, the ABL protein is always active. ABL is a kinase that activates a cell-signaling pathway that results in cell proliferation. When ABL is always active, cell proliferation occurs even without activation of the signaling pathway.

How does activated p53 initiate apoptosis?

It activates the transcription of BAX and represses the transcription of Bcl2. P53 is a transcription factor that is activated in cells when DNA damage occurs. This transcription factor regulates genes involved in DNA repair and cell cycle arrest, and/or apoptosis. BAX proteins initiate apoptosis and Bcl2 proteins prevent apoptosis. Bcl2 normally inhibits the activity of BAX; therefore, when apoptosis is necessary, Bcl2 is repressed so that BAX can activate apoptosis.

What function of zip code binding protein (ZBP1) was demonstrated in mouse fibroblasts?

It blocks translation of actin mRNAs and interacts with motor proteins to localize the mRNAs to the cell periphery. When the mRNAs have reached the cell periphery, ZBP1 is phosphorylated by Src, which blocks its interaction with the mRNA and allows translation initiation. ZBP1 blocks translation by preventing the interaction between the two subunits of the ribosome.

What role does Dicer play in the RNAi pathway?

It cleaves double-stranded RNA into 22 nucleotide siRNAs. 1. These siRNAs associate with the RISC complex, which unwinds the double-stranded RNA that base pairs with its complementary target mRNA. 2. RISC complex cleaves the target mRNA, which is rapidly degraded.

Select the three statements that are true of genomic imprinting.

It is a type of monoallelic expression (MAE). It results in a parent-of-origin pattern of expression. Epimutations can cause heritable changes in gene activity.

A woman inherited one mutant copy of the BRCA1 gene. When she was 40 years old, she developed breast cancer. In her breast tumor cells, both copies of the BRCA1 gene were mutated. This phenomenon is called:

Loss of heterozygosity. The woman's normal somatic cells are heterozygous for this mutation and a second mutation in the other allele occurred in the cells that became cancerous and formed a tumor. This loss of heterozygosity can occur through a deletion, mutations, or chromosomal rearrangements.

How is p53 activated?

MDM2 dissociates from p53 and p53 is phosphorylated and acetylated. When MDM2 binds to p53, it inactivates p53.

In general, mutations in genes that code for cell-adhesion molecules, cytoskeleton regulators, and proteolytic enzymes lead to which feature of malignant cancer cells?

Metastasis Mutations in genes encoding proteolytic enzymes and proteins that form the extracellular matrix and basal lamina, structures that prevent the migration of cells, can give cells the ability to metastasize.

Long noncoding RNAs (lncRNA) loci are often classified by their relationship to nearby protein-coding genes. Which of the following is NOT a class of lncRNAs?

Monoallelic The four types of long noncoding RNA (lncRNA) are: antisense, intronic, bidirectional, and intergenic.

RNAi is being developed as a pharmaceutical agent to treat genetic diseases. A disease caused by which of the following mutations would be the best target for an RNAi treatment?

Overexpression of one allele of a gene RNAi causes degradation of a target mRNA; short interfering RNA (siRNA) could be designed to target the overexpressed gene and reduce the amount of mRNA in the cell and potentially treat the disease.

Which of the following mechanisms is an example of posttranslational regulation?

Phosphorylation of a protein by a kinase. Addition of a phosphate group to a protein can either activate or inactivate the protein. Other posttranslational modifications: - cleaving a protein to activate/inactivate it. - covalent additions of molecules to a protein.

Some mRNAs are not translated immediately, but stored for later translation. What must happen to an mRNA for it to be translationally dormant?

Poly-A-specific ribonuclease (PARN) must shorten the poly-A tail. When the poly-A tail is shortened, it has decreased interactions with PABP, which destabilizes the poly-A tail's interaction with eIF4G (translation factor necessary for translation initiation).

In a cancer cell that has a ras oncogene:

Ras always has GTP bound. Normally, Ras is active when it has GTP bound, a state that is activated by the presence of a growth factor. Active Ras stimulates a signaling pathway that activates transcription factors that ultimately promote the cell cycle. Oncogenic Ras cannot hydrolyze GTP --> GDP and is always in the active state.

One form of myotonic dystrophy is caused by a trinucleotide expansion in the 3'UTR of the DMPK gene. How does this mutation lead to disease?

The DMPK mRNA sequesters splicing factors that are needed for alternative spicing of other genes. The DMPK mRNA is retained in the nucleus and binds proteins involved in alternative splicing. The disease phenotype is not caused by the mutant DMPK protein itself but rather by the unregulated splicing of many other muscle and nerve genes caused by the lack of splicing factors, which are sequestered by the mutant DMPK mRNA.

Beckwith-Wiedemann syndrome (BWS) is a disorder of imprinting that can cause prenatal overgrowth including high birth weight and enlarged organs. It results from abnormal patterns of DNA methylation of genes on chromosome 11, where an imprinting control region (ICR) separates and controls the expression of two genes, insulin-like growth factor 2 (IGF2) and H19. Which of the following correctly describes the regulation of IGF2 and H19 in one form of BWS?

The ICR on both the paternal and maternal chromosomes are methylated, both IGF2 alleles are active, and both H19 alleles are silent.

Which of the following statements is NOT accurate regarding epigenome projects and databases?

The NIH Roadmap Epigenomics Project was established to compare epigenetic mechanisms in various animal cells and models. The NIH Roadmap Epigenomics Project was established to elucidate the role of epigenetic mechanisms in HUMAN biology and disease. The project has two main goals: (1) provide a set of at least 1,000 reference epigenomes in a range of cell types from healthy and diseased individuals, and (2) delineate the epigenetic differences in conditions such as Alzheimer disease, autism, and schizophrenia.

Which of the following is NOT true of DNA methylation?

The enzymes that catalyze the transfer of a methyl group are called histone acetyltransferases. The enzymes that catalyze the transfer of a methyl group are called DNA methyltransferases (DNMTs), NOT histone acetyltransferases (HATs).

How can intron retention lead to negative mRNA regulation?

The mRNA could be targeted for degradation by the nonsense-mediated decay pathway. If the retained intron contains a premature stop codon, then the mRNA becomes a target for NMD pathway. mRNAs with a premature termination codon are targeted for rapid decay by the NMD pathway. If the retained intron is translated, it could lead to a different protein isoform, but it would not lead to negative regulation of the mRNA.

Select three major epigenetic mechanisms.

There are three major epigenetic mechanisms: (1) reversible modification of DNA by the addition or removal of methyl groups; (2) chromatin remodeling by the addition or removal of chemical groups to histone proteins; and (3) regulation of gene expression by noncoding RNA molecules.

Where do miRNAs originate?

They are transcribed from a cell's genomic DNA by RNA pol II.

Some long noncoding RNAs (lncRNAs) contain miRNA response elements (MREs). What is the function of these MREs?

They compete with mRNAs for miRNA binding leading to increased translation of the mRNA. The MRE is complementary to the miRNA and sequesters the miRNAs away from their target mRNA. Without the miRNA to either target the mRNA for degradation or inhibit translation of the mRNA, translation of that mRNA increases. miRNAs normally function to inhibit translation of an mRNA. Without miRNAs to bind the target mRNA, translation would increase.

Which of the following is NOT a class of short noncoding RNAs (ncRNAs)?

X inactive specific transcript (Xist) Short noncoding RNAs (ncRNAs) include three classes: microRNAs (miRNAs), short interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs).

Xist and Tsix.

Xist (X inactive specific transcript) and Tsix (Xist spelled backward) are lncRNAs that are sense and antisense transcripts of the same gene (transcribed in opposite directions). Xist is expressed on the inactivated X chromosome. Tsix is expressed on the active X chromosome.

Which finding provides the LEAST support for environmental induction of epigenetic change?

Young boys exposed to extensive air pollution have DNA base pair mutations that affect their offspring and subsequent generations. Base pair mutations are heritable changes in DNA, not epigenetic changes. Environmental agents that cause epigenetic change in the developing fetus are most likely to lead to heritable altered patterns of gene expression that can be passed onto offspring and increase disease risk in future generations.

histone modification

acetylation of H3K9 can promote "open" configuration

Kinases are proteins that:

add a phosphate group to proteins. They catalyze the addition of a phosphate group to serine, threonine, or tyrosine AA side chains in a protein.

Burkitt lymphoma is caused by a chromosome translocation. In an individual patient, all cancer cells have the same chromosome breakpoints; however, different patients have different chromosome breakpoints. This observation supports the idea that tumor cells:

arise from clonal expansion. clonal cells have a common ancestor that acquired a break point, which is now the same is all cells of a tumor.

long noncoding RNAs

can act as decoy, adapter, guide, or form enhancer-like loops

Which of the following is NOT an epigenetic mechanism that can cause chromosome-associated heritable changes to gene expression?

changing the sequence of genomic DNA

The transition between G2 and M phase of the cell cycle happens when:

cyclin B and CDK1 are present and form an active complex. Cyclin levels increase during G2 and forms a complex with CDK1.

DNA methylation

groups bound to CpG island in promoter can silence gene transcription

If a microRNA (miRNA) is partially complementary to a target mRNA:

if a microRNA (miRNA) is partially complementary to a target mRNA, translation of the target mRNA is inhibited. If a miRNA is COMPLETELY complementary to a target mRNA, the target mRNA is cleaved and degraded, but if the miRNA is only PARTIALLY complementary to the target mRNA, then the miRNA blocks translation of the mRNA.

P53 is a transcription factor involved in the DNA damage response and cell cycle arrest. Under normal conditions, p53:

is ubiquitinated by Mdm2 and targeted for degradation by the proteasome.

In Drosophila, the sex lethal (SXL) protein:

leads to alternative splice site use on the tra gene and a functional TRA protein. Sxl is only expressed in FEMALES due to transcription factors that are only found in sufficient quantities in females. SXL binds to a splicing silencer on the tra gene leading to the use of an alternative splice site that excludes a premature termination codon and leads to a functional TRA protein. Males: premature termination codon is retained in tra gene and TRA protein is nonfunctional. *Presence of the TRA protein leads to a female-specific isoform of the DSX protein and female differentiation.

If an mRNA with a premature stop codon is translated, it creates a truncated protein that can be harmful to the cell. What mechanism does a cell have for preventing accumulation of these truncated proteins?

mRNAs with a premature stop codon are targeted for degradation by the nonsense-mediated decay (NMD) pathway.

short noncoding RNAs

miRNAs and siRNAs can repress gene expression

All cells in a tumor:

originated from a common ancestor cell.

Radiation works as a cancer therapy because it:

preferentially causes damage to rapidly dividing cells. This damage to DNA and other cellular components triggers apoptosis or other forms of cell death. Radiation can damage any cell whether it is a cancer cell or not, which is why this type of treatment often causes side effects by damaging normal cells that rapidly divide (ie: intestinal lining).

The 5' cap of an mRNA

protects the mRNA from 5'-3' degradation by XRN1. When the mRNA is targeted for degradation, deadenylation causes the recruitment of decapping enzymes, which remove the 5' cap. Without the 5' cap, the mRNA can be degraded by the 5'-3' endoribonuclease XRN1.

Protein A is hormone-dependent transcription factor. A dominant mutation in protein A that causes activation of transcription without the presence of the hormone leads to activation of the cell cycle. The wild-type gene for protein A is an example of an:

proto-oncogene. Proto-oncogene is a normal gene that stimulates the cell cycle, When proto0oncogenes acquire gain-of-function mutations such that they are always active or abnormally expressed, the gene becomes an oncogene.

Adenosine-uridine rich elements (AREs) found in the 3' UTR of some mRNAs:

regulate the stability of mRNA. AREs bind RNA binding proteins that either recruit mRNA degradation proteins and stimulate mRNA decay or block mRNA degradation proteins and stabilize the mRNA.

Processing bodies (P bodies) are:

sites where non-translating mRNAs accumulate. Processing bodies contain high concentrations of mRNA decay proteins including decapping proteins and exoribonucleases, and thus are thought to be places of mRNA degradation Translation does not occur in processing bodies. Processing bodies store mRNAs that are not actively being translated.

Histones are NOT typically modified by the addition of which of the following groups?

sulfhydryl Over 20 different chemical modifications can be made to histones, but the major changes include the addition of acetyl, methyl, and phosphate groups.

Heterogenous ribonucleoproteins (hnRNPs) are:

trans-acting factors that inhibit splicing.

RNA interference (RNAi) prevents:

translation of a gene. During RNA interference, short double stranded RNAs target a specific mRNA for degradation in the cytoplasm. Degrading the mRNA prevents translation of the gene. RNAi occurs in cytoplasm.

A benign tumor becomes a malignant tumor when the

tumor has the ability to invade other tissues and form secondary tumors.