Chapter 19: Epigenetics Quiz

How does acetylation of lysine affect its interaction with DNA, and how is this related to the activation of gene expression?

Acetylation of the lysine side chain removes its positive charge, preventing the ionic interaction with phosphate and decreasing the interaction between the histone and the DNA. As a result, genes are more accessible and able to be expressed.

What is the evidence that epigenetic changes are involved in cancer?

All cancers tested thus far have exhibited a pattern of global hypomethylation, although specific regions are hypermethylated. The genes that are silenced include tumor suppressors.

The period of greatest susceptibility to diseases resulting from epigenetic changes is ______________________.

Before birth

How does an environmental factor like stress generate a response that is transmitted from generation to generation?

Environmental factors induce epigenetic changes in genes that result in certain types of behavior. Since it has been shown to be heritable, it is believed that the influence of environmental factors can also be passed on to subsequent generations.

Imprinting disorders do not involve changes in DNA sequence, but only the methylated state of the DNA Does it seem likely that imprinting disorders could be treated by controlling the maternal environment in some way, perhaps by dietary changes?

Evidence suggests that maternal nutrition does not largely influence global methylation patterns, particularly in nutrient-replete populations; however, an important impact on gene-specific methylation is observed.

A developmental disorder in humans called spina bifida is a neural tube defect linked to a maternal diet low in folate during pregnancy. What does this suggest about the cause of spina bifida?

Folic acid is used by the body in several important processes including serving as a methylation precursor. Low levels of this substance are correlated with occurrence of the disorder, which suggests that spina bifida is a(n) epigenetic disorder with a(n) environmental root.

Even though cancer genomes are overall hypomethylated, explain why some genes are hypermethylated in cancer cells.

Hypermethylation of promoters will lead to reduced expression of the correspondent genes. Some genes such as DNA repair genes and cell cycle stop genes need to be expressed. When they are not expressed, this can lead to cancer.

What are the similarities and differences between short ncRNAs and long ncRNAs

Long: prevent transcription by chromatin remodeling, forming chromosomal loops, etc, interact with chromatin regulators Short: interact with RISC, silence the targeted messages by cleaving them or by blocking translation Both: operate by forming complexes, act as guides for RNA-protein complexes

Amino acids are classified as positively charged, negatively charged, or electrically neutral. Which category includes lysine?

Lysine is a positively charged amino acid.

A child with PWS comes to your clinic for a diagnosis of the molecular basis for this condition. The gel below shows the results of testing with short tandem repeats (STRs) from the region of chromosome 15 associated with the disorder. Is this case caused by a deletion in the paternal copy of chromosome 15?

No, the disorder was not caused simply by a deletion in the paternal copy of chromosome 15. If this were the case, the gel results for the patient would show a single, maternal STR allele and no paternal STR allele.

Spinal bifida - Does this exclude genetic mutations as a cause of this condition?

No, this does not exclude genetic causes. While taking folic acid prevents many cases of spina bifida, it does not prevent all of them.

How does the positive charge of lysine allow it to interact with DNA?

Positively charged lysine side chains can form ionic bonds with negatively charged phosphate groups in the DNADNA backbone.

What are the three classes of monoallelic gene expression?

Random inactivation of the X chromosome Random inactivation of autosomal genes Genomic imprinting

How can the role of epigenetics in cancer be reconciled with the idea that cancer is caused by the accumulation of genetic mutations in tumor-suppressor genes and proto-oncogenes?

The accumulation of genetic mutations in tumor-suppressor genes and proto-oncogenes changes their expression or causes the production of nonfunctional products. Epigenetic modifications can also change gene expression and, therefore, can cause cancer.

Identical twins each carry the same genome, but over time, can develop different phenotypes. How can you explain this?

The environmental exposures lead to differences in their epigenome and, therefore, differences in gene expression.

Several mechanisms are involved in epigenetic modifications to the genome that regulate gene expression, and epigenetic control of gene expression is important in development, cancer, and modulating the genomic response to environmental factors. How do we know how methylation of promoters silences gene expression?

The methyl groups sit in the major groove and prevent binding of transcription factors and other proteins needed to form an initiation complex.

How can you reconcile the differences in modification?

The result of the third methylation of lysine 79 may depend on the interaction of this modified amino acid with other modified residues.

Are these overlaps explained by different modifications?

Yes, except the third methylation of lysine 79, which can result in either activation or repression.

Spinal Bifida - Should researchers be looking for mutant alleles of genes that control formation and differentiation of the neural tube?

Yes, it may increase our understanding of not only spina bifida but also many other conditions that result from neural tube defects.

Are there any overlapping modifications?

Yes, modification of lysine residues 9, 27, and 79 can cause either activation or repression of expression.

What are the major mechanisms of epigenetic genome modification?

chromatin remodeling long noncoding RNAs binding to chromatin-modifying enzymes histone modification involving, acetyl, methyl, and phosphate groups binding of RISC to target mRNA molecules DNA methylation

What are the differences and similarities among the three classes of monoallelic gene expression? Genomic imprinting:

is dependent on the parent that contributed the allele is found in less than 1 percent of the genome and usually found in clusters

What are the differences and similarities among the three classes of monoallelic gene expression? Inactivation of the autosomal genes:

is found in only some cells, resulting in a mosaic pattern of expression in an individual is found in 15-20 percent of genes

What are the differences and similarities among the three classes of monoallelic gene expression? Inactivation of the X chromosome:

is mediated by the coordinated expression of two antisense lncRNAs occurs only in females the entire chromosome is inactivated

From the data in the table, which histone H3 modifications are associated with gene activation?

lysine 79, lysine 4, lysine 27, lysine 14, lysine 36, lysine 9

What are the differences and similarities among the three classes of monoallelic gene expression? All classes of monoalleleic gene expression:

once a gene has been inactivated, it remains inactive in that individual involves the inactivation of one of the two inherited alleles

Which H3 modifications are associated with repression?

serine 10, lysine 9, lysine 79, lysine 27

Choose the two types of ncRNAs involved in epigenetic control of gene expression.

short ncRNA and long ncRNA

What functions of lncRNAs in epigenetic regulation? 1) They can bind __________ , effectively sequestering them from target genes (__________ ) 2) The can facilitate the assembly of proteins that will then act to regulate gene expression (__________) 3) They can recruit __________ to the DNA in an allele-specific fashion (__________) 4) They can induce chromosome looping to allow for gene regulation (__________ )

transcription factors; the decoy strategy the adapter strategy chromatin remodeling complexes; the guide strategy the enhancer strategy

A child with PWS comes to your clinic for a diagnosis of the molecular basis for this condition. The gel below shows the results of testing with short tandem repeats (STRs) from the region of chromosome 15 associated with the disorder. Based on your interpretation of the data, what is the cause of PWS in this case? Why?

uniparental disomy; loss of the paternal copy of chromosome 15 Because the banding pattern in the patient's sample matches that of his mother and includes both maternal STR alleles