Epigenetics: Chromatin, DNA Methylation, Avy Locus, and Environmental Influences

Flashcards cover epigenetics basics, chromatin structure and chromatin states, DNA methylation (5mC) generation and removal, CpG islands, Avy allele structure and coat-color outcomes, and how diet/environment can influence epigenetic status in offspring.

What is epigenetics?

Non-sequence dependent, heritable changes in gene expression that can occur within cell lineages and, in some cases, be transmitted to subsequent generations.

What are the main components of chromatin?

DNA wrapped around histone proteins forming nucleosomes, plus linker histone H1 and non-histone chromatin proteins; higher-order structure and remodeling complexes influence condensation.

What is the effect of chromatin condensation on transcription when it occurs near promoter regions?

Increased condensation near promoters generally represses transcription by limiting access of the transcriptional machinery to DNA.

How do heterochromatin and euchromatin differ in terms of gene expression and nuclear localization?

Heterochromatin is highly condensed and transcriptionally repressed, often located at the nuclear periphery; euchromatin is less condensed and transcriptionally active, located more internally.

What is 5-methyl cytosine (5mC) and where is it typically found?

A DNA base modification at CpG dinucleotides, added by DNA methyltransferases; found at promoters (CpG islands) and repetitive elements, influencing gene expression and genomic stability.

How is 5mC generated in the genome?

De novo methylation by DNMT3A/B and maintenance methylation by DNMT1 after DNA replication.

How is 5mC removed or demethylated?

Active demethylation via TET enzymes (5mC to 5hmC, 5fC, 5caC) followed by base excision repair; or passive demethylation through replication without maintenance methylation.

Where in the genome are CpG islands, and how does their methylation relate to gene expression?

CpG islands are GC-rich regions near promoters; unmethylated CpG islands are associated with active transcription, while methylation represses transcription.

What is the Agouti viable yellow (Avy) allele and its structural feature?

Avy contains an intracisternal A particle (IAP) retrotransposon insertion upstream of the Agouti gene, providing an ectopic promoter whose activity is modulated by methylation.

How does methylation of the Avy IAP promoter affect coat color in mice?

Hypomethylation of the Avy IAP LTR leads to ectopic Agouti expression and yellow fur; hypermethylation silences the ectopic promoter, producing pseudoagouti (brown) fur.

What coat color phenotypes do Avy mice show and why?

A spectrum from yellow to pseudoagouti (brown) due to variable epigenetic methylation of the Avy locus, demonstrating epigenetic variegation.

Why can genetically identical Avy mice have different coat colors?

Because the epigenetic state (DNA methylation) at the Avy locus varies among individuals, affecting Agouti expression despite identical DNA sequences.

How do diet and environmental agents influence the epigenetic status of offspring?

Maternal diet and environmental exposures can alter DNA methylation patterns at CpG islands in offspring through altered methyl donor availability and other signaling mechanisms.

What nutrients or factors are commonly involved in altering methylation status during development?

Methyl donors and cofactors such as folate, choline, methionine, and B vitamins; exposure to certain environmental agents can also affect methylation patterns.

What is transgenerational epigenetic inheritance?

The transmission of epigenetic marks or gene expression states across generations beyond direct exposure, without changes to the underlying DNA sequence.