One histone modification that is seen consistently inmany species is the addition of an acetyl group to thetwelfth lysine in the H4 protein. If you were a geneticist working on yeast and had a clone of the H4 gene,what could you do to test whether the acetylation atthis specific lysine was necessary for the functioningof chromatin?
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One histone modification that is seen consistently in
many species is the addition of an acetyl group to the
twelfth lysine in the H4 protein. If you were a geneticist working on yeast and had a clone of the H4 gene,
what could you do to test whether the acetylation at
this specific lysine was necessary for the functioning
of chromatin?
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- Look at the two yeast colonies in Figure Q4–3. Eachof these colonies contains about 100,000 cells descendedfrom a single yeast cell, originally somewhere in the mid-dle of the clump. A white colony arises when the Ade2 geneis expressed from its normal chromosomal location. Whenthe Ade2 gene is moved to a location near a telomere, itis packed into heterochromatin and inactivated in mostcells, giving rise to colonies that are mostly red. In theselargely red colonies, white sectors fan out from the middleof the colony. In both the red and white sectors, the Ade2 gene is still located near telomeres. Explain why white sec-tors have formed near the rim of the red colony. Based onthe patterns observed, what can you conclude about thepropagation of the transcriptional state of the Ade2 genefrom mother to daughter cells in this experiment?Drosophila geneticists have isolated many mutationsthat modify position-effect variegation. Dominantsuppressors of variegation [Su(var)s] cause less frequent inactivation of genes brought near heterochromatin by chromosome rearrangements, whiledominant enhancers of variegation [E(var)s] causemore frequent inactivation of such genes.a. What effects would each of these two kinds of mutations have on position-effect variegation of thewhite gene in Drosophila (that is, would the eyesbe more red or more white)?b. Assuming that these Su(var) and E(var) mutationsare loss-of-function (null) alleles in the corresponding genes, what kinds of proteins do youthink these genes might encode?Let’s suppose you have isolated chromatin from some bizarreeukaryote with a linker region that is usually 300–350 bp inlength. The nucleosome structure is the same as in other eukaryotes.If you digested this eukaryotic organism’s chromatin with ahigh concentration of DNase I, what would be your expectedresults?
- Give at least one example of a chromosomal structureor function affected by the following mechanisms formodulating chromatin structure:a. Posttranslational changes of the normal histonesfound in the nucleosomea. What DNA sequences are found at the telomeresof human chromosomes?b. What functions do the two telomere-associatedcomplexes, telomerase and shelterin, fulfill at chromosome ends?c. Where do you think that the RNA component oftelomerase comes from?An interesting phenomenon found in vertebrate DNAis the existence of pseudogenes, nonfunctional copiesof a gene found elsewhere in the genome. Some pseudogenes appear to have originated as double-strandedDNA copies of mature mRNA inserted into the chromosome; these copies later underwent mutations tomake them into pseudogenes.a. What sequence information might provide cluesthat the original source of some of these pseudogenes is cDNA copied in cells from mRNA andthen inserted into the genome?b. Would this mechanism of generating pseudogenesbe more likely to have operated if the pseudogenewas part of a gene family clustered in one region ofthe genome, or if it was instead part of a genefamily whose members are scattered around thegenome? Explain
- . The physicist Stephen Hawking, famous for his theories about black holes, has lived past the age of 70 withamyotrophic lateral sclerosis (ALS), a paralyzing neurodegenerative disease that is usually fatal at a muchyounger age. Recently, geneticists discovered that amajor cause of ALS is the unusual expansion of ahexanucleotide repeat (5′-GGGGCC-3′) that lieswithin a gene called C9ORF72, at a location outside ofthe gene’s open reading frame (ORF). A single expanded allele is sufficient to cause ALS, but the reasonthe disease allele is dominant remains unclear. Someexperimental results support the theory that the allelemakes a toxic RNA containing the expanded repeat. Ifthis theory is correct, in what ways is the mutant ALScausing allele similar to the mutant allele that causesHuntington disease? In what ways is it similar to themutant allele that causes fragile X syndrome?Which of the following is likely to be transcriptionally expressed? euchromatin and DNA with methyl groups euchromatin DNA with methyl groups DNA with acetylated histones euchromatin and DNA with acetylated histonesThe cells from a person’s malignant tumor were subjected to insitu hybridization using a probe that recognizes a unique sequenceon chromosome 14. The probe was detected only once in each ofthe cells. Explain this result, and speculate on its significance withregard to the malignant characteristics of these cells.
- If histones are acetylated on a lysine amino acid (an epigenomic mark), are genes in this region likely to be expressed or not? Briefly, in a sentence or two, explain your answer. (Hint: In your answer explain what the DNA and chromatin structure would look like in regions with the acetylation compared to regions without).. For each of the terms in the left column, choose thebest matching phrase in the rigf. satellite DNA 6. small basic proteins that bind toDNA and form the core of thenucleosomeg. chromatin 7. complex of DNA and proteinswhere spindle fibers attach to achromosomeh. cohesin 8. beadlike structure consisting ofDNA wound around histoneproteinsi. histones 9. protein complex that protectstelomeres from degradation andend-to-end fusionsj. shelterin 10. regions of a chromosome thatare distinguished by stainingdifferencesht column.a. telomere 1. protein complex that keepssister chromatids togetheruntil anaphaseb. G bands 2. origin of replication in yeastc. kinetochore 3. repetitive DNA found near thecentromere in higher eukaryotesd. nucleosome 4. specialized structure at the endof a linear chromosomee. ARS 5. complexes of DNA, protein, andRNA in the eukaryotic nucleusTwo circular DNA molecules, which we can call molecule A andmolecule B, are topoisomers of each other. When viewed under theelectron microscope, molecule A appears more compact than molecule B. The level of gene transcription is much lower for molecule A. Which of the following three possibilities could accountfor these observations?First possibility: Molecule A has three positive supercoils, andmolecule B has three negative supercoils.Second possibility: Molecule A has four positive supercoils, andmolecule B has one negative supercoil.Third possibility: Molecule A has zero supercoils, and molecule Bhas three negative supercoils.