Epigenetics slide show flash cards

Define epigenetics.

The study of heritable changes in gene expression that do not involve modifications to the DNA sequence itself.

How do histone acetyltransferases (HATs) affect gene expression?

HATs add acetyl groups to histone tails, leading to a loosely packed chromatin structure, which facilitates transcription factor binding and gene activation. This is associated with increased transcription.

What is the role of histone methyltransferases (HMTs)?

HMTs add methyl groups to specific histone residues, which can either silence or activate genes depending on the precise context of the methylation.

How does DNA methylation performed by DNMTs generally affect gene expression?

DNA methylation by DNMTs adds methyl groups to cytosine bases, leading to tight packing of nucleosomes, inhibiting transcription, and resulting in gene repression.

Name two human syndromes that highlight the influence of epigenetic modifications on phenotype.

Angelman Syndrome and Prader-Willi Syndrome.

What is dosage compensation?

Dosage compensation refers to the equal expression of X-linked genes between males (XY) and females (XX), achieved through X-inactivation in females.

What is genetic mosaicism in the context of X-inactivation?

Genetic mosaicism occurs when different cells exhibit different genetic expressions based on which X chromosome is active, due to the random silencing of one X chromosome in females.

When do epigenetic changes typically occur?

Epigenetic changes occur during oogenesis, spermatogenesis, or early embryonic development.

What are the three specific molecular modifications (epigenetic marks) described?

1. Histone Acetylation 2. Histone Methylation 3. DNA Methylation.

What is the purpose of X-inactivation in mammals?

To equalize X-linked gene expression among males and females by silencing one of the two X chromosomes in females.

What is a Barr body?

The inactivated X chromosome condenses into a Barr body, which is observable in the nucleus of female somatic cells.

How does nutrition (royal jelly) influence bee castes?

The type of nutrition (royal jelly) affects gene expression, showing an epigenetic influence on development, leading to phenotypic differences between queen and worker bees.

Define genomic imprinting.

Imprinted genes exhibit a non-Mendelian pattern of inheritance, where genes are marked by methylation so that only one allele (maternal or paternal) is expressed.

What is the mechanism of genomic imprinting?

Imprinting involves alterations to DNA, typically by methylation, without changing the DNA sequence itself, leading to monoallelic expression.

Give an example of a gene that exhibits genomic imprinting and its function.

The Igf2 gene, responsible for growth hormone production. A mutant allele can lead to dwarfism.

What are the characteristics of Prader-Willi Syndrome (PWS)?

Reduced motor function, obesity, small hands and feet.

What are the characteristics of Angelman Syndrome (AS)?

Hyperactivity, unusual seizures, thinness, repetitive muscle movements, and intellectual disabilities.

What causes Angelman Syndrome (AS) if inherited from the mother?

A deletion in a specific region of chromosome 15, which suppresses the UBE3A gene, leads to AS if inherited from the mother.

What causes Prader-Willi Syndrome (PWS) if inherited from the father?

A deletion in a specific region of chromosome 15, which suppresses the SNRPN gene, leads to PWS if inherited from the father.

What is the significance of chromatin remodeling in epigenetics?

Chromatin remodeling influences gene accessibility and expression; it can lead to various levels of gene silencing, from specific gene silencing to the silencing of entire chromosomes.

How many X chromosomes do typical female and male mammals possess?

Typical females have two X chromosomes (XX), while typical males have one X chromosome (XY).

Describe the mechanism of X-inactivation in placental mammals versus marsupials.

In placental mammals, the choice of which X chromosome to silence is random and passed on during subsequent cell divisions. In marsupials, the paternally contributed X chromosome is preferentially silenced.

What are the distinguishing characteristics of Queen Bees?

Queen Bees are larger, have a lifespan over several years, mate once, and can produce up to 2000 eggs per day.

What are the distinguishing characteristics of Worker Bees?

Worker Bees are smaller, sterile, have a lifespan measured in weeks, and produce royal jelly during early stages of development.

When does genomic imprinting become established and how is it maintained?

Genomic imprinting is established during meiosis and is maintained in somatic cells through mitosis.

Explain what 'heritable changes' means in the context of epigenetics, differentiating it from genetic mutations.

In epigenetics, 'heritable changes' refers to modifications in gene expression that can be passed down to daughter cells during cell division (mitosis) or even across generations (meiosis), without altering the underlying DNA sequence itself. This contrasts with genetic mutations, which are permanent alterations to the DNA sequence.

Describe the specific molecular outcome of histone acetylation that leads to gene activation.

Histone acetylation by HATs adds acetyl groups to positively charged lysine residues on histone tails. This neutralizes the positive charge, reducing the electrostatic attraction between histones and the negatively charged DNA. The loosened chromatin structure makes the DNA more accessible, allowing transcription factors and RNA polymerase to bind to gene promoters and initiate transcription.

Elaborate on the mechanism by which DNA methylation leads to gene repression, specifically mentioning its impact on nucleosome packing and transcription factor access.

DNA methylation by DNMTs adds methyl groups to cytosine bases, typically in CpG islands within gene promoter regions. This can directly inhibit the binding of transcription factors. Additionally, methylated DNA can recruit methyl-binding proteins (MBPs) and histone deacetylases (HDACs), which lead to a more condensed, 'tightly packed' chromatin structure (tightening of nucleosomes), further sterically hindering access for transcription machinery and repressing gene expression.

How does the randomness of X-inactivation in placental mammals contribute to genetic mosaicism at a cellular level?

In placental mammals, the choice of which X chromosome to inactivate (maternal or paternal) is random in each cell during early embryogenesis. Once inactivated, that specific X chromosome remains silenced in all subsequent daughter cells. This random inactivation leads to different cell populations within the same female individual expressing predominantly genes from either the maternal or paternal X chromosome, resulting in a mosaic phenotype at the cellular level.

Explain how a single deletion on chromosome 15 can lead to two distinct syndromes, Angelman Syndrome and Prader-Willi Syndrome, depending on parental origin.

Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS) are both caused by a deletion in the same region of chromosome 15 (15q11-q13), but their distinct phenotypes arise due to genomic imprinting. If the deletion is inherited from the mother, the maternally expressed UBE3A gene is lost, leading to AS. If the deletion is inherited from the father, the paternally expressed SNRPN gene (and others in the region) is lost, leading to PWS. This emphasizes that the expression of these genes is 'imprinted,' meaning only one parental allele is normally active, and the loss of that active allele results in the specific syndrome.