20: Transcrp. Reg. 5: Epigenetics (review Qs are starred)

1. Gene expression complexes that repress expression recruit histone writers that designate repression
2. histone code readers propagate the signal
3. the signal recruits a DNA methylase
4. DNA methyl binding proteins are recruited and establish a methylation pattern
5. methylation pattern can be inherited

So basically, the histones get methylated, then the DNA gets methylated.

• It's when some genes have only the maternal or paternal copy expressed, not both. 
• During mom or dad's gamete formation, the methylation pattern of both grandpa and grandma's allele is erased.  Then the methylation pattern may be re-established, depending on whether sperm or eggs are made.
• DNA methylation patterns of one parent are not lost during fertilization! 

• It binds an insulator element.  When bound, the insulator prevents the effect of the enhancer.
• If the DNA in the insulator element is methylated, the insulator cannot bind, so the enhancer can work and transcription is turned on.
• In this example, imprinting activates genes.

• Deamination of methylated C results in T, which is not recognized by the DNA repair system, so CG dinucleotides are rare in vertebrates.
• Those that remain are not evenly distributed but exist as CpG islands.
• CpG island are frequently found near housekeeping genes, because they are active and should not be turned off by methylation.
• When looking at transcripts, you'll often find CpG islands in the 5' (promoter region) end.

1. It's a non-DNA based phenotypic change--expression of a gene is unchanged, but the gene products are doing something different.
2. ***The prion state is dominant.  Normal protein that gets made in cells with the prion gets rapidly converted to Prion form. 
3. It's species specific at the protein level.  If a species doesn't make the protein, the prion won't affect it.
4. One example is the prion form of Sup35 in yeast.  When it's in the prion form, translation does not stop at stop codons!

1. positive feedback (new gene expression inherited)
2. histone modification (new chromatin state inherited)
3. DNA methylation (new DNA methylation state inherited)
4. Protein aggregation state (prions: new protein conformation state inherited)

A mechanism to give balance of X-chromosome products to Autosomal chromosome products in both sexes.

It's about the ratio of X:A!

1. Flies: Male X is hyperactivated (double expression of male X)

1. C. Elegans (worms): Female Xs both downregulate--whole chromosome hypoactivation (Half expression of two female Xs)

1. humans: One X is (nearly) completely repressed-- (near) whole chromosome inactivation by condensation (one inactive female X)

• X-inactivation
• Inactivation is random so females are genetic mosaics
• messes with coat color in cats and mice

1. synthesis of RNA from the XIC (X-inactivation center) locus
2. That RNA, called Xist RNA, coats the X chromosome from which it was transcribed
3. The coated X chromosome is called a Barr Body

A bunch of other stuff happens, too.

1. During mitosis, chromosomes have to line up due to homology, homologous regions need to find each other.
2. Some genes are necessary as double copies.  These genes are similar to genes on the Y chromosome.

• They're regions of the X chromosome and the Y chromosome that are very similar.
• Those regions still have the same functional genes and still cross over
• Pseudo-A regions do not dosage compensate, and are still accessible.
• XO, XXX, and XXY organisms have too much or too little pseudo-A product, so there is some degree of "sickness" in non-XX or non-XY mammals.

• Variegation (sectors or clones with different phenotypes in the same organ) caused by the inactivation of a gene in some cells through its abnormal juxtaposition with heterochromatin
• Changes chromatin state!
• Often has a lot to do with transposable elements

1. Drosophila: White transgene insertions into or near transposable elements result in variegated eyes
2. Mice: IAP retrotransposon affects color expression in mice.  differing levels of agouti depending on where the retrotransposon popped in
3. Morning glory flowers: DNA methylation of a non-autonomous MuLE transposon can spread to the promoter of a flower-color gene (Dfr-B), creating petal-color streaks
4. Maize, TE family, epialleles, Mutator transposon, spotted tissue on leaves.