Epigenetics V: Modes of Epigenetic Inheritance Flashcards
What is the preferred substrate for DNMT1 in vitro?
Hemi-methylated DNA
DNMT1 associates with sites of DNA ______________ in S phase via PCNA interaction
Replication
DNMT1 associates with which protein that binds specifically to hemi-methylated DNA?
UHRF1
What helps direct DNMT1 action and can re-inforce DNMT1 function by recruiting UHRF1?
H3K9 methylation
Polycomb protein complexes PRC1 and PRC2 regulate one another through (positive/negative) feedback
Positive
What domain of PRC2 methylates K27 and modifies K27?
Ezh2 methylates K27 and Eed modifies K27
What domain of SUVAR39 methylates K9 and modifies K9?
Chromodomain modifies K9 and SET domain methylates K9
What happens to histones during DNA replication?
Daughter DNA strands carry a combination of old and new nucleosomes
Copying mechanism occurs from previously (unmethylated/methylated) histones to (unmethylated/methylated) histones
Methylated (old); unmethylated (new)
What ensures that new histones use old histones as a template?
Interaction between old histones and components of the replication machinery
What composes the PCR2 dinucleosome?
One monomer that is unmodified and one monomer that already has H3K27me
Which subunit is bound to H3K27me3 nucleosome and which subunit is bound to unmodified nucleosome?
Eed; Ezh2
Which nucleosome activates the enzymatic activity of the complex?
Eed bound to H3K27
What experiment was done to observe transgenerational epigenetic inheritance?
Expose parent to stress or change of nutrition and measure physiological effect on the parent to see if it was passed on to future generations
Which of the following corresponds to either transgenerational or intergenerational inheritance?
a. Due to transmission of an epigenetic change to gametes independently of the initial exposure
b. Due to initial, direct exposure of gametes in F0
a. Transgenerational
b. Intergenerational
Transposon insertion in color gene promoters and variable DNA methylation in transposon are models to study (intergenerational/transgenerational) epigenetic inheritance
Transgenerational
How does low maternal care lead to CpG methylation in the promoter of the gene for glucocorticoid receptor in the hippocampus in pups?
Low maternal care leads to blocked transcription factor binding, which contributes to low levels of glucocorticoid receptors and high corticosterone levels in pups
True or false: Changes in paternal diet/metabolism do not affect sperm and health of offspring
False
Are DNA methylation and histone modifications mechanisms for transgenerational effects transmitted through the male germline?
No
What could be mechanisms for transgenerational effects transmitted through the male germline?
Small RNAs, metabolites, microorganisms
Why are histone modifications not a mechanism for transgenerational inheritance?
Most histones are removed and replaced with protamines in the late stages of sperm development
piRNAs are involved in what mechanism?
Silencing transposons in the germline
What is the role of small RNAs in transcriptional silencing and epigenetic inheritance?
Forming heterochromatin
Which small RNAs don’t affect transcription and act on highly repetitive sequences?
siRNAs; piRNAs