M1-Lecture 2 Flashcards by Aaron Hagos

What leaves a chemical “signature” on the genes that determines whether & how the genes are expressed.

Experiences

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Different genotypes respond to environmental stimulus differently? T/F

TRUE

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The three components that make up a phenotype:

Epigenetics, Environment, and Genetics.

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Give example of SNPs:

SNP mutation resulting in gene variants that can influence sensitivity to one’s environment.

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Example of Epigenetics:

microRNA and ncRNA

CpG methylation

Histone modification

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Example of environment:

Nutrition, toxins, drugs, pathogens

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Embryonic stem cell divisions:

Mesoderm: middle layer

Endoderm: Internal layer

Ectoderm: External layer

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How did the cells in our body become different & why do they stay like that?

Once specialized, the changes are permanent.

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DNA not always in chromosome form but open? T/F

TRUE

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Modifying the histone will expose the DNA? T/F

TRUE

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What are the factors that affect epigenetic mechanisms:

Development (utero, childhood)

Environmental chemicals

Drugs/pharmaceuticals

Aging

Diet

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Mention a few epigenetic modifications:

DNA methylation

Histone modification

Chromatic accessibility

Non-coding RNA regulation

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What is an epigenetic factor found in some dietary sources:

Methyl group

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DNA methylation function:

Can tag DNA and activate or repress genes.

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Blank are proteins around which DNA can wind for compaction and gene regulation.

Histones

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What alters the extent to which DNA is wrapped around histones & availability of genes in DNA to be activated?

Epigenetic factors (which can give rise to health endpoints).

For instance, increased histone acetylation generally leads to a more open chromatin structure, facilitating gene expression, while DNA methylation typically silences genes by promoting a closed chromatin configuration.

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Biological dogma states that genetics regulates all inherited traits across generations, & epigenetic modifications are reset upon passage of germ line? T/F

TRUE

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What is responsible for the functional use & stability of the genetic info our chromosomes hold & connects genotype to phenotype.

Epigenome

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Epigenetic inheritance occurs through meiosis and several generations, including trans-generational? T/F

TRUE

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The nucleosomes of DNA and histones are organized into what:

Chromatin

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Change to the structure of chromatin influences gene expression: T/F

TRUE

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Epigenetic modifications - when is a gene “switched on”:

Active “open” chromatin
Unmethylated cytosines [bases in DNA] (white circles)
Acetylated histones (adding acetyl group to lysine residues on histone proteins) reduces + charge on histones for relaxed and open chromatin structure for gene transcription.

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Epigenetic modifications: when is a gene “switched off”

Silent (condensed) chromatin
Methylated cytosines (red circles)
Deacetylated histones

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Types of histone modifications:

Acetylation
Methylation
Sumoylation
Phosphorylation
Ubiquitination

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Define the types of histone modification:

Acetylation: adding acetyl group to lysine (found in histone tails) residues on histones (makes chromatin open) Methylation: addition of methyl groups to lysine/arginine (found in the tails of histone) residues on H (activate/repress gene expression) Note: depends number of methyl added & specific residues affected. Phosphorylation: adding phosphate group to serine, threonine, or tyrosine residues on H, affecting chromatin structure, gene e. common in cell divi. & DNA damage repair. Ubiquitination: addition to H. influence chromatin s. & gene expression, histone degradation or altering chromatin dynamics. Sumoylation: addition of SUMO to H, impact chromatin structure & gene expression, gene silencing.

In condensed nucleosomes, histones are methylated and unacetylated. T/F

TRUE

Uncondensed nucleosomes, histones are unmethylated & acetylated. T/F

TRUE

Active vs. inactive regions of chromatin:

Active chromatin: unmethylated DNA & acetylated histones. Inactive chromatin: Methylated DNA & deacetylaed histones

An epigenetic tag (methylated vs. unmethylated) is placed on targeted DNA, marking it with a special status that activated or silences genes? T/F

TRUE

DNA methylation or unmethylation are reversible modifications and benefit?

Specific genes can be expressed or silenced genes based on deve. or biochemical cues, such as changes in hormone levels, dietary components or drug exposures.

What does histone code hypothesis state:

Activity of chromatin region depends on degree of chemical modification of histone tailes.

What enzymes place acetyl groups on histone?

Acetyltransferases

What enzyme removes acetyl groups from histones?

histone deacetylases

Methyl groups are placed on DNA by what?

DNA methyl transferases

Demethylation of DNA can either be passive (through replication process) or active or both? T/F

TRUE

Methylated promoters & enhancers keep genes inactive? T/F

TRUE

What proves epigenetic inheritance?

Enzymes methylate DNA in the same spot on new cells.

70-90% of all CpG dinucleotides exist in methylated form? T/F

TRUE

CpG islands demonstrated methylation variability. T/F

TRUE

DNA methylation occurs often at CpG sites. T/F

TRUE

These sites are embedded in in genome in discrete (terminal CpG islands) 0.5-0.2 kb, in the adjacent regions of transcriptional start sites.

CpG sites

More than half the genes in the genome contain CpG islands within their promoter & are usually unmethylated in normal cells (house-keeping genes, which are always on). T/F

TRUE

Methylation marks occur throughout embryological deve.? T/F

TRUE

Methylation of promoters & enhancers prevent RNA polymerase from binding to the promoter and blocks gene activity? T/F

TRUE

DNA methylation is a component of one-carbon metabolism pathway and depends on enzymes & dietary micronutrients cofactors, including folate, choline and betaine. T/F

TRUE

See diagram on

One Carbon Metabolism Pathway

Genes can have multiple tissue specific enhancers? T/F

TRUE

DNA methylation - Blank maintains DNA methylation pattern through cell devisions in proliferating cells.

DNMT1

DNA methylation - Blank is responsible for establishing new DNA methylation patterns during development?

DNMT3a/b

Examples of cells in our body that divide rapidly?

Hair follicle cells, GI tract (vomiting), and RBC and WBC.

Sequence-specific molecules that guide protein complexes to specific sites in the chromatin for transcriptional repression.

Long non-coding RNA (IncRNA)

IncRNA has important role in X-chromosome inactivation, imprinting. T/F

TRUE

What are small RNA molecules (22 nucleotides)?

miRNA

miRNA are post-transcriptional regulators of gene expression? T/F

TRUE

How do miRNA regulate gene expression?

By binding to mRNAs and promoting their degradation or inhibiting their translation

Examples of Non-coding RNAs:

miRNA and circRNAs

What are covalently closed & circular-shaped subgroup of ncRNAs?

circRNAs

circRNAs are known as the major epigenetic regulators of pathogenesis? T/F

TRUE

How do circRNAs regulate gene expression?

By sponging microRNAs, binding to proteins or they can be translated into proteins themselves.

Blank is central mechanism driving normal development & programming.

Epigentics

List and explain epigenetic mechanisms:

1. Histone modification: Either acetylation or methylation. Affect how tightly DNA is wrapped around histones & regulate gene expression. 2. DNA methylation: adding methyl groups to DNA, cytosine bases, silencing genes by preventing transcription machinery from accessing DNA. 3. Non-coding RNAs: RNA molecules that do not code for proteins, like microRNAs & Long non-coding RNAs. Regulate gene expression by interacting with mRNA & chromatin.

Blank refers to erasure & remodelling of epigenetic marks.

Epigenetic reprogramming

Developmental stages in which epigenome undergoes profound programming?

1. Pre-implantation - De-methylation - X-chromosome inactivation - Tissue-specific methylation (morphogenesis) 2. Gametogenesis - De-methylation - X-chromosome activation - Imprinting

Diet-induced phenotypic change: Blank refers to changes in maternal diet can produce changes in DNA methylation that can affect the phenotype of the offspring.

Agouti gene

Although agouti gene is dominant, mothers fed (folate, choline, & betaine) - donate methyl group} did not produce young expressing the phenotype. T/F

TRUE

In pregnant rats, a low protein diet predisposes the pups to diabetes, hypertension, & obesity. T/F

TRUE

Rat starved in vetro, express PPARalpha in their liver that leads to greater fat storage. T/F

TRUE

PPARalpha helps with metabolism and conserve. T/F

TRUE

Temperature is not the only factor in sex determination. T/F

TRUE

Injection of estrogen in turtle eggs generates females, regardless of temp.? T/F

TRUE

High levels of aromatase is linked with formation of ovaries. T/F

TRUE

Aromatase activity or its expression may be temp dependent. T/F

TRUE

What pathways are activated when honyebees are fed royal jelly (royal actin which binds EGFR)?

TOR and MAPK pathways

TOR AND MAPK PATHways increase body size & acceletates development, as well as Juvenile hormone (JH) that promotes ovary deve.

TRUE

Honeybees have methylated DNA like vertebrates - Dnmt3. T/F

TRUE

Reducing Dnmt3 promotes the frequency of queens? T/F

TRUE

Characteristics of genes rarely methylated:

Less fearful Modest HPA responses to stress

Characteristics of genes highly methylated:

Fearful heightened HPA responses to stress

Stress hormones affect DNA methylation? T/F

True

Tactile stimulus (licking & grooming) regulates synthesis of glucocorticoid receptor in hippocampus? T/F

True

The binding sites for transcription factor NGF-1 (enhancer for glucocorticoid receptor gene) is methylated 1 day but is lost if licked & groomed. What does this mean?

Rats that receive lots of licking & grooming, have more GR in the brain & are able to deal with stress.

Maternal behavior of low grooming is carried to the next generation. T/F

True

Intergenerational Effects:

Maternal environmental exposures (F0) have direct effects on germ cells/developing fetus (including germ line of fetus, altering phenotype [F1] and possibly grandchild [F2], or the paternal line, father's exposure has direct effects on germ cells that form the child.

Trangenerational effects:

Epigenetic information is transmitted across generation, but can only be proved if effect is transmitted to F2 (for maternal & paternal line in which exposure occured only before conception. or F3 (on maternal line when exposure occurs during pregnancy) or future generations.

Epigenetic leads to structural changes during the period of gestation? T/F and give example.

True Example: Epigenetics can result in altered organ structure leading to Brain sparing - so most of our oxygen & nutrient delivery goes toward the brain (based on the size of the arrow) Also, this may lead to fetal hypoxia and placental dysfunction.

Besides structural changes, epigenetics also consists of cellular aging, altered homeostatic endpoints? T/F

True

Homeostasis does not involve keeping conditions static, it involves keeping conditions within tightly regulated physiological tolerance limits? T/F

True

Earlier intervention improves functional capacity & responses to new challenges? T/F

True

What does intervention look like in the context of DOHaD?

Education Pre-conception, Pre-natal and Post-natal support Investment in children and families

M1-Lecture 2 Flashcards

(90 cards)