Ch 16: gene regulation in eukaryotes - epigentics

3 abnormalities in chromatin modification that are common in cancer cells

1. DNA methylation: hypermethylation of CpG islands 2. Covalent modification of histones: increase expression of oncogenes and decrease expression of tumor suppressor genes 3. chromatin remodeling: abnormalities in the locations of nucleosomes

what may PRC1 do to inhibit gene expression

1. chromatin compaction 2. covalent modification of histones 3. direct interaction with a transcription factor

Following X-chromosome inactivation, most of the genes on the inactivated X chromosome are silenced. Explain how. Name one gene that is not silenced.

After the Xist RNA coats the X chromosome, it recruits proteins that silence genes, such as DNA methyltransferase, and proteins that make the chromosome more compact to form a Barr body. One gene on Xi that is not inactivated is the Xist gene.

what are different types of epigenetic regulation

DNA methylation, chromatin remodeling, covalent histone modification, localization of histone variants, feedback loop

example of genomic imprinting in mammals

Igf2 gene

Which Igf2 gene (from the father or mother) is expressed

Igf2 gene from the father

2 types of PcG

PRC1 and PRC2

how might gene repression occur by PcG?

PRC2 binds to a polycomb response element which leads to the trimethylation of lysine 27 on H3 --> prevents binding of RNA pol or recruits PRC1

which protein complex is important for gene repression - TrxG or PcG?

PcG (polycomb gene repression) rePression = Pcg

Let's suppose a mutation removes the ICR next to the Igf2 gene. If this mutation is inherited from the mother, will the Igf2 gene (from the mother) be silenced or expressed? Explain.

The Igf2 gene inherited from the mother will be expressed. For silencing to occur, a loop must form. The loop could not form if the ICR was missing.

With regard to development, what would the dire consequences be if polycomb group complexes did not function properly?

The consequences would be that many genes would be expressed in cell types where they should not be expressed. This would cause ab-normalities in development and would likely be lethal.

How can environmental agents that do not cause gene mutations contribute to cancer? Would these epigenetic changes be passed to offspring?

Though they don't change the DNA sequence, epigenetic modifications can affect gene expression. Such changes could increase gene expression and thereby result in oncogenes or they could inhibit the expression of tumor suppressor genes. Either type of change could contribute to cancer. For example, DNA methylation of a tumor sup-pressor gene could promote cancer.

Which protein complex is important for gene expression - TrxG or PcG?

TrxG (trithorax grp, gene activation) eXpression = TrXg

Xist is expressed from the (active or inactive) x chromosome. Tsix is expressed from the (active or inactive) x chromosome

Xist = inactive Tsix = active

what 2 genes are important in x chromosome inactivation

Xist and Tsix

When mice carrying the Avy allele exhibit a darker coat, this phenotype is thought to be caused by dietary factors that result in a. a greater level of DNA methylation and a decrease in the expression of the Agouti gene. b. a lower level of DNA methylation and a decrease in the expression of the Agouti gene. c. a greater level of DNA methylation and the overexpression of the Agouti gene. d. a lower level of DNA methylation and the overexpression of the Agouti gene.

a

which gene is expressed prior to x chromosome inactivation? a. Tsix gene b. Xist gene c. Both the Tsix and the Xist d. neither the Tsix or the Xist

a. Tsix gene

how can DNA methylation be transmitted by cis- epigenetic mechanisms?

after DNA replication - each strand is hemimethylated via maintenance methylation (routine event). If another copy of the same gene in the cell was not methylated - it would need to undergo de novo methylation (not routine)

In one cell, gene C is expressed, whereas in another cell, gene C is inactive. After the cells are fused experimentally, both copies of gene C are expressed. This observation could be explained by a. a cis-epigenetic mechanism. b. a trans-epigenetic mechanism. c. DNA methylation. d. both a and b.

b

An epigenetic modification to a specific gene may initially be established by a. a transcription factor. b. a non-coding RNA. c. both a and b. d. none of the above.

c

which type of epigenetic modification is the Igf2 gene regulated by? (cis or trans)

cis-epigenetic regulation

The underlying cause(s) of epigenetic changes associated with cancer may be a. mutations in genes that encode chromatin-modifying proteins. b. environmental agents that alter the function of chromatin-modifying proteins. c. mutations in genes that encode proteins that directly accelerate cell growth. d. all of the above. e. both a and b.

e

what is true about cis modifications? a. don't affect expression of the same gene located elsewhere b. affect multiple copies of the gene (if multiple are present) c. they are proteins and ncRNA's d. maintained only at that particular site e. both a and d

e. both a and d

What are the contrasting roles of trithorax and polycomb group complexes during development in animals and plants?

he trithorax and polycomb group complexes are involved with gene activation and gene repression during development, respectively. They cause epigenetic changes that allow genes to remain either active or permanently repressed. Such changes occur during embryonic development and are maintained during subsequent stages.

where does methylation of the Igf2 gene occur?

imprinting control region (ICR) and differentially methylated region (DMR)

do epigenetic modifications involve a change in the DNA sequence

no

Are queen and worker bees genetically different from each other

no not at the genetic sequence however, their epigenetic modifications are different

x chromosome inactivation

process that occurs in female mammals in which one of the X chromosomes is randomly turned off in each cell

What does the agouti gene do?

promotes the synthesis of yellow fur pigment in mice

epigenetics

study of mechanisms that lead to changes in gene expression that can be passed from cell to cell and are reversible

association

suggest that the 2 variables follow a pattern

epigenetic changes may be caused by these environmental agents

temperature, diet, toxins

what happens when pluripotency factors to move to one x chromosome?

the x chromosome with the pluripotency factors is expressed while the other become silent

what happened to bee larvae injected with DNA methyltransferase inhibitor?

they became queen bees (royal jelly must have a substance that inhibits methyltransferase)

T/F: epigenetic changes that occur during embryonic development are remembered during subsequent cell divisions

true

how does diet effect honey bee development

when bees are bathed in royal jelly (made by nurse bees) during larval stage and fed it into adulthood, they become queens rather than workers

what 2 protein complexes are recognized for epigenetic changes by regulating genes encoding transcription factors

*TrxG (trithroax grp) *PcG (polycomb gene)

how are epigenetic changes targeted to specific genes

*transcription factors bind to a specific gene and initiate epigenetic modifications *ncRNA act as a bridges b/w specific sites in the DNA and proteins that alter chromatin or DNA structure

Can epigenetic changes be inherited?

yes - they are passed from parent to offspring

List and briefly describe five types of molecular mechanisms that may underlie epigenetic gene regulation.

1. DNA methylation—the attachment of methyl groups to cytosines in DNA. This often silences transcription. 2. Covalent histone modification—the covalent attachment of groups to the amino terminal tails of histones. This may silence or activate genes. 3. Chromatin remodeling—changes in the positions of nucleosomes. This may lead to a closed or open conformation for transcription. 4. Histone variants—replacement of standard histones for histone variants. This may silence or activate genes. 5. Feedback loop—the activation of a gene encoding a transcription factor. After the transcription factor is made, it continues to activate its own expression as well as the expression of other genes.

what are 3 reasons that describe the association between epigenetics and human disease

1. epigenetic changes directly contribute to disease symptoms 2. disease symptoms may arise first and then they cause subsequent epigenetic changes to happen 3. association is indirect because a third factor is involved (factor that causes both the disease and epigenetic changes even though those epigenetic changes do not contribute to the disease)

process of x chromosome inactivation

1. x chromosomes pair up and a symmetry break causes the pluripotency factors and CTCFs to move to one x chromosome (remains active and expresses Tsix) 2. the other x chromosome (without the pluripotency factors) expresses the Xist gene 3. Xist RNA binds to Xic and spreads to both ends. Xist RNA recruits proteins that cause this X chromosome to become more compact and be inactive

For XCI to occur, where are the Xist and Tsix genes expressed? a. Xist is expressed only on Xa, and Tsix is expressed only on Xi. b. Xist is expressed only on Xi, and Tsix is expressed only on Xa. c. Xist is expressed only on Xa, and Tsix is expressed only on Xa. d. Xist is expressed only on Xi, and Tsix is expressed only on Xi.

b

For the Igf2 gene, where do de novo methylation and maintenance methylation occur? a. De novo methylation occurs in sperm, and maintenance methylation occurs in egg cells b. De novo methylation occurs in egg cells, and maintenance methylation occurs in sperm cells. c. De novo methylation occurs in sperm, and maintenance methylation occurs in somatic cells of offspring d. De novo methylation occurs in egg cells, and maintenance methylation occurs in somatic cells of offspring

c

correlation coeffecient

compares two variables to see if they are related to each other

Epigenetic changes may a. be programmed during development. b. be caused by environmental changes. c. involve changes in the DNA sequence of a gene. d. be both a and b.

d

Which of the following possibilities could explain how PcG complexes are able to silence genes? a. The compaction of nucleosomes b. The attachment of ubiquitin to histone proteins c. The direct inhibition of transcription factors, such as TFIID d. All of the above

d

Which of the following types of epigenetic changes may promote cancer? a. DNA methylation b. Covalent modification of histones c. Chromatin remodeling d. All of the above

d

why is the Igf2 gene inherited from the father but not the mother

de novo methylation during sperm formation but not egg formation - methylation prevents binding of CTC binding factor and can then be stimulated by the enhancer

cancer

disease characterized by uncontrolled cell division

When does X chromosome inactivation occur?

during embryogenesis

XIC portion of the x chromosome

encodes 2 genes: Xist and Tsix that are transcribed in opposite directions

tumor suppressor genes

exhibit a decrease in expression in cancer cells. Proteins help prevent cancer. A decrease in their expression may allow cancer to occur

which of the following are examples of molecular changes that can have an epigenetic effect on gene expression? a. chromatin remodeling b. covalent histone modification c. localization of histone variants d. DNA methylation e. feedback loops f. all of the above

f

T/F epigenetic changes during development are not maintained by epigenetic regulation

false

genomic imprinting

gene regulation in which an offspring expresses the copy of a gene from one parent but not both

oncogenes

genes that overactive in cancer cells - abnormally high level of expression that cause cellular changes that promote cancer

3 examples of epigenetic gene regulation as programmed developmental changes

genomic imprinting, x chromosome inactivation, cell differentiation

In X-chromosome inactivation, when is the choice made as to which X chromosome is inactivated? Does this choice occur in embryonic cells, in adult somatic cells, or both?

the choice only occurs during embryonic development

how is the agouti gene representative of environmental impact on epigenetic changes

when fed a diet with chemicals that increase DNA methylation, offspring had darker fur (consistent with the methylation of Agouti gene inhibits the gene). Darkness of fur correlated with level of DNA methylation of CpG islands in the TE