Flashcards in Lecture 14 - Epigenetics Inheritance and Imprinting Deck (61)
What is a big example of epigenetics?
Paternal lifestyle choices leading to obesity and T2D (eg: high fat diet) are passed on as beta cell dysfunction (aka glucose intolerance) to female progeny by passing on methylation patterns of 77 insulin and glucose metabolism genes
What is the classic definition of epigenetics?
Information that is passed from one generation to the next (either to daughter cells during division or from parent to offspring) but is NOT encoded in the primary DNA sequence
What is the epigenome?
Range of modifications to the genome (DNA) that ensure the stable transmission of gene expression patterns without changes to the DNA sequence
What are epigenetics disruptors?
Factors that influence our epigenetic inheritance patterns
What is genomic imprinting? Purpose?
The ability to mark a gene as coming from either the father or mother with different methylation patterns
To be able to only express one allele
What 4 diseases are associated with epimutations and genomic imprinting?
1. Beckwith-Wiedemann syndrome
2. Prader-Willi syndrome
3. Angelman syndrome
What is a transgenerational phenotype?
The effect of multigenerational exposure in subsequent generations (F3 and beyond)
In pregnant females, in what generations can environmental exposure cause epigenetic modifications? What is this called?
In the next two generations (F1 and F2) through the fetus and its germ line
In males, in what generations can environmental exposure cause epigenetic modifications?
Multigenerational exposure in males is limited to the F0 and F1 generations
What is the basic and main mechanism of epigenetics?
Methylation of cytosine in DNA to form 5-methyl cytosine
What is particular about cytosine methylation in vertebrates?
Confined to cytosines in a CG sequence
What is 5-methylcytosine comparable to?
Mix between T and U
Product of deamination of 5-methylcytosine?
How are methylation patterns retained during DNA replication?
Maintenance methyl transferases recognize methylation patterns on the parent strand and replicate it on the daughter strand following DNA replication
What are the 3 maintenance methyltransferases?
1. DNA methyltransferase 1 (DNMT 1)
2. DNA methyltransferase 3A (DNMT3A)
3. DNA methyltransferase 3B (DNMT3B)
What is another name for maintenance methyltransferases?
Methyl-directed methylating enzyme
How does DNA methylation affect gene expression? Explain how it works.
It contributes to mechanisms of stable gene REPRESSION because it provides binding sites for DNA methyl-binding proteins that will prevent the DNA from being accessed, thereby silencing it
How are repressive chromatin structures usually formed? 2 steps
1. Histone writer protein attracks histone readers
2. A de novo DNA methylase is attracted by the histone readers and methylates nearby cytosines in DNA
3. Methylated DNA is then bound by DNA methyl-binding proteins
Can histone modification patterns be inherited? How?
Histone writer enzymes are inherited and reproduced the pattern
What is the leaky gene hypothesis?
Under normal circumstances genes are upregulated due to some signal and when we want to downregulate it, we remove the gene activator or add a repressor (or both). This slows down gene expression, but it's not completely turned off, demonstrating the leaky behavior to the expression of these genes.
How can we completely turn a gene off instead of just down-regulating it?
What triggers DNA methylation?
Cell no longer produces activating transcription factors => gene regulatory proteins and transcription machinery dissociates from DNA => DNA methylation
Following the binding of DNA methyl binding proteins, how else is the DNA further silenced? 2 ways
1. Recruitment of chromatin remodeling complexes
2. Recruitment of histone deacetylases
By what fold can DNA methylation affect the rate of gene expression in different tissues?
1 million fold
In what organisms does genomic imprinting occur?
Does genomic imprinting affect all genes in mammals?
NOPE, only a few
Describe the steps of genomic imprinting from germ cell formation to offspring. What can this cause?
1. Genomic imprinting is removed from somatic cells in germ cells, followed by meiosis
2. Female genes NOT imprinted, males genes are through methylation
=> Different imprinting patterns can cause phenotypic differences in the progeny even if they carry exactly the same DNA sequences of the two gene alleles
What provides an important exception to classical genetic behavior?
Describe genomic DNA methylation in embryonic development. 3 steps
1. Following fertilization, first the paternal genome is ACTIVELY demethylated prior to the first cleavage division
2. Maternal demethylation occurs through a PASSIVE mechanism after several cleavage divisions
3. De novo methylation occurs in the inner cell mass (ICM) cells, which later differentiate into the embryo