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Flashcards in Epigenetics Deck (17):

Implications of DNA Methylation and Where it Occurs

-inhibits transcription
-usually found around transcription start sites
-methylation occurs on CpG islands on cytosine
-CpG islands attract transcriptional repressors
-correct expression of tissue-specific gene and X activation relies on DNA methylation


Bisulfite-Mediated Conversion of DNA

-upon separation and treatment with bisulfite, umethylated Cs become Us
-can use PCR to amplify
-DNA pol turns U into T on OT strand, and complementary to that will be A
-All of the Ts that you will see will show that they are unmethylated Cs and all of the Cs that remain in the OT strand represent methylated Cs
-Can use this to map the methylation of the promoter



Restriction enzymes that recognize the same sequence






Uses SAM to add methyl groups to DNA


DNA Methylation Patterns in Development

Paternal genes are actively demethylated immediately upon fertilization
Maternal methylation is passively diluted
This occurs to make cells totipotent during cleavage, so this differentiation is 'written' by CpG islands

Methylation occurs during implantation

Denovo methylation occurs rarely after gastrulation, but this phenomenon is seen frequently in cancer


Rett Syndrome

-progressive neurologic developmental disorder
-X-linked dominant
-period of apparently normal development 6-18 mo
-life expectancy ~40 yrs
-MECP2 gene mutations are the cause of most cases of Rett syndrome



-capable of binding specifically to methylated DNA
-represses transcription from methylated promoters
-ubiquitously present, most expressed in brain
-loss of function in differentiated post-mitotic neurons likely results in inappropriate overexpression of gene with potentially damaging effects during CNS maturation
-MECP2 is like a nucleus for repression, it becomes a scaffold for other proteins to bind


Genomic Imprinting

While most autosomal genes are expressed roughly equally from the two parental alleles, imprinted genes are expressed preferentially or completely from only one allele (paternal or maternal) depending on the specific imprinted gene under consideration.

Imprinted genes play vital role in embryonic growth, neonatal behavior, tissue/developmental-stage specific monoallelic expression patterns

Methylated imprinted genes DO NOT become demethylated during methylation reprogramming in preimplantation

Prader-Willi and Angelman Syndromes***



Growth promoting hormone during gestation
Exerts its effects by binding to IGF-1 receptor
IGF2 may also bind to IGF-2 receptor (maternal gene), which acts as signaling ANTAGONIST
-This gene was imprinted by paternal line
-can bind many receptors

-deleting mother's IGF2 receptor gene results on large offspring
-deleting father's IGF-2 ligand gene produces dwarf offspring
-deleting mother's receptor gene and father's ligand gene produces normally sized offspring


Beckwith-Wiedermann Syndrome

Activation of maternal IGF2 ligand gene causes larger offspring


What can be done to N-termini of histone tails?

Acetylation of K
Phosphorylation of ser
Methylation of K and R


Long ncRNA

Function in
-chromatin remodeling
-transcriptional regulation
-post-transcriptional regulation
-precursors for siRNA
-Tsix (negative regulator of Xist)



LncRNA that is transcribed fromm Xic on inactive chromosome (Xi)
-Xist RNA covers the entire chromosome and silences gene expression via epigenetic modification of histones and DNA


Establishment of XIC

1. Pre-Xic
-both chromosomes will express Xist in low []s
2. Establishment of XIC
-one X chromosome will begin to express Tsix in high levels. This leads to huge reduction in Xist in this chromosome, making this the active X chromosome.


Phenotypic Plasticity

-ability of one genotype to produce more than 1 phenotype when exposed to different environments

Examples: Environmental effects (diet, stress) on phenotype may involve epigenetic changes in gene function

Adult neuronal plasticity and neurogenesis-- changes in chromatin marks and transcriptional networks associated with sustained neuronal activity, mood disorders, and addiction


Nutrition and Epigenome example: Agouti Gene

Normal mice have methylated variable methylation region ahead of agouti gene, causes brown fur

Methyl-deficient mice have active Agouti gene, leading to yellow fur, obesity, diabeeetus