Final Exam Genetics

3. What three molecular mechanisms alter chromatin structure and are responsible for many epigenetic phenotypes?

(1) changes in DNA methylation; (2) chemical modifications of histone proteins; and (3) RNA molecules that affect chromatin structure and gene expression.

process of genomic imprinting

-DNA is methylated to turn off specific genes

example of epigenetic effects in monozygotic twins

-DNA methylation/histone acetylation in identical twins is similar early in life but vary significantly in older twins

example of epigenetic effects of early stress in humans

-childhood abuse brains had more methylation of glucocorticoid receptor gene than those who did not experience abuse -growing up in low socioeconomic environment bfore age 5 altered expression of genes related to immune function of adults (eg alteration of telomere length)

example of transgenerational epigenetic effects on metabolism

-male mice fed a low protein diet: offspring had increased expression of genes involved in lipid and cholesterol metabolism and corresponding decrease in levels of cholesterol -male mice fed high fat diet: daughters developed diabetes-like condition as adults, alteration of 642 genes in insulin-secreting pancreatic islet cells

example of epigenetic effects of environmental chemicals

-molecular analysis revealed different DNA methylation patterns (exposure led to increased DNA methhylation) between test and control groups exposed to vinclozolin (fungicide used in wine industry linked to reduced sperm production)

example of epigenetic changes induced by maternal behavior

-offspring of mothers who display more affection (licking and grooming offspring) are less fearful as adults and show reduced hormonal responses to stress -difference in groomed/non-groomed rats disappeared after brains of young rats were infused with deacetylase inhibitor (prevents removal of acetyl groups from histone proteins)

how is chromatin structure altered?

1. DNA methylation: addition of methyp groups to nucleotide bases, CpG dinucleotides, CpG islands 2. histone modifications: phosphates, methyl groups, acetyl groups, ubiquitin 3. RNA molecules: X inactivation by Xist, siRNAs that direction DNA methylation/histone modifications (silence genes and transposable elements)

process of X inactivation

1. both Xa and Xi chromosomes have Xist gene 2. Xist gene on Xi is transcribed into lncRNA (long noncoding RNA) which attracts PRC2 and PRC1 (polycomb repressor complexes) and coats one X chromosome to create epigenetic mark (histone 3 lysine 27 trimethylation H3K27me3) that suppresses transcription through histone methylation and methylation of CpG dinucleotides

What 3 molecular mechanisms alter chromatin structure and are responsible for many epigenetic phenotypes?

1. changes in DNA methlyation 2. chemical modifications of histone proteins 3. RNA molecules that affect chromatin structure and gene expression

What is the major form of DNA methylation that is seen in eukaryotes? At what type of DNA sequence is DNA methylation usually found?

5-methylcytosine. In eukaryotes, DNA methylation is often seen at CpG dinucleotides. In plants, DNA methylation is also frequently seen at CpNpG trinucleotides.

4. What is the major form of DNA methylation that is seen in eukaryotes? At what type of DNA sequence is DNA methylation usually found?

5-methylcytosine. In eukaryotes, DNA methylation is often seen at CpG dinucleotides. Additionally, in plants, DNA methylation is also frequently seen at CpNpG trinucleotides.

2. What are the important characteristics of an epigenetic trait?

An epigenetic trait is one that is stable and passed on to cells or offspring but does not involve changes to the DNA base sequence. Many epigenetic traits are caused by changes in gene expression resulting from modifications to chromatin. Although stable, many epigenetic traits can be influenced by environmental factors.

22. Epigenetics has been described as "inheritance, but not as we know it." Do you think this is a good definition? Why or why not?

Answers will vary. Yes, it is a good definition. In Mendelian inheritance, differences in the DNA nucleotide sequences between alleles cause the differences in in phenotypic expression from those alleles. The inheritance pattern of the alleles as well as the alleles present determines the phenotypic expression. Epigenetics involves the inheritance of phenotypes without changes in DNA sequences. Chemical modification of DNA nucleotides within an individual can produce gene expression patterns that can be passed down to subsequent generations. Essentially, phenotypes seen within parents due to epigenetic markers can be transmitted to their offspring. No, it is not a good definition. Epigenetic inheritance is part of what parents can contribute to their offspring, and we are beginning to understand how epigenetic markers are inherited and how they can influence inheritance. It is just part of the parental contribution to their offspring. Additionally, epigenetic changes are not as stable as DNA nucleotide sequence changes. A change in the environment for the offspring can lead to changes in epigenetic markers and subsequently changes in gene expression.

What would be the effect on X inactivation of adding siRNAs that eliminated the products of Xist gene?

Both X chromosomes would be active.

What would be the effect on X inactivation of adding siRNAs that eliminated the products of Xist?

Both X chromosomes would be active.

methylated C turns into

C (don't change at all)

Changes in ___________ _____________ affect the Expression of Genes

Chromatin Structure

Epigenetic Changes result from

DNA methyaltion

RITS recruits _______ ____________ _______

DNA methylating enzymes

epigenetics decribes the changes in________ and __________ that are heritable

DNA modification, chromatin structure

Chromatin Structure can be changed by modifying _________ and _____________

DNA, Histones protein

Early development is controled by

Egg Polarity genes

23. What would be required to prove that a phenotype is caused by an epigenetic change?

Epigenetic effects are traits that are heritable in the sense that they are passed on to other cells or across generations. So, a first step would be to show that the phenotype was stable across cell divisions or generations. To rule out direct environmental effects, it would be important to make sure that the environments of individuals with and without the trait were the same. A second step would be to show that the phenotype is not the result of differences at the nucleotide sequence level. This would require isolating the gene associated with the phenotype and demonstrating that its DNA sequence was the same in individuals who have the phenotype and individuals who do not have it. A third step would be to find differences in chromatin structure or DNA methylation in individuals with and without the phenotype. A final step might be to alter the chromatin or DNA structure experimentally and show that this alteration results in the appearance of the phenotype.

Neutralize postive charges on histones tail lead to DNA unpacking

Euchromatin

Epigenetic Changes in Gametogenesis Result in _____________ _______________

Genomic Imprinting

Transposable elements

Have a transposes-inverted repeats- direct repeats. Can also hop around randomly and cause gene activation and reactivation during the course of development.

____________ proteins can be chemically modified

Histones

Euchromatin

Histones are modified

Heterochromatin

Histones are not modified

17. Define genomic imprinting

In genomic imprinting, the sex of the parent that contributed the allele to the offspring determines if the expression of the transmitted allele occurs within the offspring.

How are induced pluripotent stem cells derived from adult somatic cells?

Induced pluripotent stem cells are generated by treating cultured fibroblast cells with a cocktail of transcription factors that cause extensive epigenetic reprogramming to the treated cells, including changes in methylation patterns and histone modifications.

What are induced pluripotent stem cells?

Induced pluripotent stems result when adult somatic stem cells are induced to dedifferentiate and revert them to stem cells.

Transcriptional silencing

Methylation of DNA leads to altering chromatin structure and inhibition of transcription.

how is DNA methylation transmitted across cell division?

Methyltransferase enzymes recognize the hemimethylated state of CpG dinucleotides following replication and add methyl groups to the unmethylated cytosines, resulting in two new DNA molecules that are fully methylated.

Briefly explain how patterns of DNA methylation are transmitted across cell division.

Methyltransferase enzymes recognize the hemimethylated state of CpG dinucleotides following replication and add methyl groups to the unmethylated cytosines, resulting in two new DNA molecules that are fully methylated.

7. What types of histone modifications are responsible for epigenetic phenotypes?

Modification of histone proteins especially in the positively charged tail are responsible for many epigenetic changes. The histone modifications include covalent modifications such as the addition or removal of chemical groups such as acetyl groups, methyl groups, phosphates, and ubiquitin to the positively charged tail. These modifications can change chromatin structure thus altering gene expression. Additionally, some modifications may change gene expression through their effect on the recruitment of transcription factors.

What types of histone modifications are responsible for epigenetic phenotypes?

Modification of histone proteins especially in the positively charged tail are responsible for many epigenetic changes. The histone modifications include covalent modifications such as the addition or removal of chemical groups such as acetyl groups, methyl groups, phosphates, and ubiquitin to the positively charged tail. These modifications can change chromatin structure thus altering gene expression. Additionally, some modifications may change gene expression through their effect on the recruitment of transcription factors.

DNA methylation

Occurs at cytocines, causes heterochromatin

RNA molecules Induce Epigenetic Effects by ____________

Paramutation

Further embroyonic development is controlled by _____________ genes and ____________ genes

Segmentation, homeotic

What long-term behavioral and epigenetic effects would you expect to see in the removed rat offspring when they grow up?

The adults would show increased fear and heightened hormonal response to stress and have differences in DNA methylation and histone acetylation that altered expression of genes involved in response to stress.

How is X inactivation an epigenetic phenotype?

The change in gene expression due to the inactivated X chromosome in one cell can be passed along stably to other cells that are produced from the original cell where X inactivation occurred, which is an epigenetic effect.

how is X inactivation an epigenetic phenotype?

The change in gene expression due to the inactivated X chromosome in one cell can be passed along stably to other cells that are produced from the original cell where X inactivation occurred, which is an epigenetic effect.

What is the epigenome?

The epigenome refers to the overall nature and types of chromatin modifications possessed by an organism.

18. What is the genomic conflict hypothesis for the origin of genomic imprinting?

The genomic conflict hypothesis proposes that different and competing evolutionary forces are acting on paternal and maternal alleles. These different competing forces result in genomic imprinting differences and subsequent differences in gene expression patterns for paternal and maternally derived alleles.

5. How does DNA methylation repress transcription?

The methyl group of 5-methylcytosine sits within the major groove of the DNA and may inhibit the binding of transcription factors and other proteins required for transcription to occur; 5-methylcytosone attracts proteins that directly repress transcription. It also attracts histone deacteylase enzymes, which remove acetyl group histone proteins, altering the chromatin structure that represses transcription.

How does DNA methylation repress transcription?

The methyl group of 5-methylcytosine sits within the major groove of the DNA and may inhibit the binding of transcription factors and other proteins required for transcription to occur. 5-methylcytosine attracts proteins that directly repress transcription. It also attracts histone deacetylase enzymes, which remove acetyl group histone proteins, altering the chromatin structure that represses transcription.

21. How do epigenetic traits differ from traditional genetic traits, such as the differences in color and shape of peas that Mendel studied?

The phenotypic differences in traditional genetic traits such as the color and shape of peas that Mendel studied are due to differences in the DNA base sequences within the alleles. In epigenetics, the phenotypic differences are not due to changes in allele DNA base sequences, but are differences in the expression of genes that are passed on to other cells and sometimes to other generations.

25. What would be the effect of deleting the Dnmt3 gene in honeybees?

The silencing of the Dnmt3 gene expression results in the development of queen bees. If the Dnmt3 was deleted in honeybees, it would likely result in all female bees developing reproductive organs and becoming queen bees because the methylating enzyme could not be produced.

what would be the effect of deleting Dnmt3 gene in honeybeed?

The silencing of the Dnmt3 gene expression results in the development of queen bees. If the Dnmt3 was deleted in honeybees, it would likely result in all female bees developing reproductive organs and becoming queen bees because the methylating enzyme could not be produced.

24. Which honeybee in Figure 21.4 (the worker or the queen) will have more copies of 5-methylcytosine in its DNA? Explain your answer.

The worker bees will have more copies of 5-methylcytosine in its DNA. Queen bees have been fed royal jelly, which silences the expression of the Dnmt3 gene. The normal function of the Dnmt3 gene product is to add methyl groups to DNA. Because the queen bees lack expression of the Dnmt3 gene, their DNA will be less methylated. Worker bees however express the Dnmt3 gene resulting in more methylation.

do worker bees or queen bees have more copies of 5-methylcytosine in DNA?

The worker bees will have more copies of 5-methylcytosine in its DNA. Queen bees have been fed royal jelly, which silences the expression of the Dnmt3 gene. The normal function of the Dnmt3 gene product is to add methyl groups to DNA. Because the queen bees lack expression of the Dnmt3 gene, their DNA will be less methylated. Worker bees however express the Dnmt3 gene resulting in more methylation.

Unmethylated C turns into

U (Recongnized as "T" in DNA sequencing

What is cancer

Uncontrolled cell growth

RNA molecule regulate __ ____________

X inactivation

The X chromosome is inactivated due to the expression of genes at the

X inactivation center

20. The introduction to this chapter describes the long-term effects of diet on the residents of Överkalix, Sweden. a.What evidence suggests that these effects are due to epigenetic effects? b. What additional evidence would help to demonstrate that these changes are due to epigenetic changes?

a. Children and grandchildren from parents exposed to famine conditions in Överkalix, Sweden lived longer and were less likely to die of cardiovascular issues than children and grandchildren whose parents were not exposed to food shortages. Additionally, in children and grandchildren whose parents had abundant food there were higher incidents of diabetes and deaths associate with the effects of diabetes. The evidence suggests that environmental conditions that the grandparents experience potentially resulted in changes to gene expression of metabolic genes that was passed along to subsequent generations. b. Genetic comparisons between individuals whose ancestors were exposed to famine conditions with those individuals who ancestors were not exposed to food shortages would be useful. Differences in DNA methylation and histone acetylation patterns between these groups of individuals would be evidence supportive of epigenetic changes. Differences in gene expression patterns for certain metabolic genes between these groups would be additional evidence. DNA sequencing of genes associated with cardiovascular health and diabetes would potentially help to demonstrate if any differences are linked to nucleotide sequence differences as opposed to epigenetic changes.

DNA methylation

addition of the methyl groups to nucleotide bases

def. of induced pluripotency stem cells iPSCs

adult somatic cells that can dedifferentiate and revert to stem cells by extensive epigenetic reprogramming by iPS reprogramming factors

effect of addition of methyl groups to histones (histone methylation)

altered chromatin structure but "it depends"

Maternal expression of the _____ and ______ genes during oogenesis produces mRNA that are localized to the poles of the egg

bicoid, nanos

how are iPSCs generated?

by treating cultured fibroblast cells with a cocktail of transcription factors that cause extensive epigenetic reprogramming to the treated cells including changes in methylation patterns and histone modifications.

def. of epigenetics

changes in chromatin structure, which alter gene expression; heritable; no change in nucleotide sequence

What is translocation?

chromosomal rearrangement where a proto-oncogen ends up next to a gene that is constantly transcribed. "ends up next to a constantly transcribed gene!"

DNA repair genes

code for proteins that reduce substitution mutations (recessive). If there is a mutation here then much less goes corrected

effect of addition of acetyl groups to amino acids in histone tails (histone acetylation)

destabilization of chromatin structure and increased transcription

Through the process of ______________ a cell becomes committed to a particular cell fate

determination

Segmentation genes

determine the number and orientation of body segments

Egg Polarity genes determine the ______ ________ ______ of the embryo

dorsal ventral axis

Cellular differentation results from________________ during development

epigenetic changes

Homeotic genes

establish the identity of each segment

Normal DNA =

euchromatin

Unmethylated DNA

euchromatin

histone modified

euchromatin

RNA molecules present during early development permanently alter ___________ _______________

gene expression

Egg polarity

genes are required for the normal development of the embryo

Normal histones (+)

heterochroamtin

Methylated DNA =

heterochromatin

Removal of modifications, restores postive charges, leading to DNA packing

heterochromatin

Chromatin structures can be investigated by dectecting

histones modifications

Epigenetics

how through the process of development, a genotype produces a phenotype

__________ results in expression of alleles inherited from only _____ parent

imprinting, one

paramutation

interaction between two alleles at a single locus, whereby one allele induces a heritable change in the other allele.

Behavorial epigenetics

life experiences, especially early life, have long lasting effects on behavior

Epigenetic changes can be induced by

meternal behavior

DNA can be altered by ________. Specifically directed by __________ ____________ that affect gene expression

methylation, RNA molecules

Histone-modifying enzymes are attracted by multiple nearby __________

methylcytosines

Egg Polarity genes are expressed during __________, thus having ___________ orgin

oogenesis, maternal

Maternal expression of the dorsal gene during ____________ produces a protein that is a ____________

oogenesis, morphogen

def. of epigenome

overall pattern of chromatin modifications possessed by each individual organism

Many plant cell can _____________ cell determination

reverse

Epigenetic changes can be __________to reprogram _____ ___________ into induced pluripotent cells, which can be directed to become many_____________.

reversed, adult cells, cell types

def. of genomic imprinting

sex of the parent that transmits allele determines its expression; due to different degrees of methylation of genes inherited from parents

___________ or _________ are incorporated into a RNA Induced Transcriptional Silencing protein. Target the protein to _________ _______________ that match the ____________.

siRNA, miRNA, DNA sequences, RNA

effect of DNA methylation

suppression of gene expression b/c methyl group inhibits binding of transcriiption factors and other proteins, methyl groups attract proteins that repress transcription, DNA methylation attracts histone deacetylase enzymes, which remove acetyl groups from tails of histone proteins

Concentration gradient of _______ ________ affects the developmetal fate of the _____________

surrounding region

Telomerase gene:

telomeres shorten after every division... unless the telomerase gene has a mutation and they never shorten, resulting in cancer.

t or f: DNA methylation is maintained across cell divisions

true

t or f: histone modifications are maintained across cell divisions

true