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Epigenetics

QuestionAnswer
define epigenetics: study of changes in gene expression that occur without changes in DNA sequence. Epigenetic changes are mitotically heritable.
Epigenetic modifications must also be removable - when? Generally in germ line development to regain totipotency.
Euk? Hetero? Euk = open, Hetero = closed.
Where does Methylation occur in mammals? at CpG dinucleotides.
What lays down methylation in mammals? de novo methyltransferases - DNMT3A and DNMT3B.
WHich 3 main regions does methylation occur in? CpG islands - methylation synonomous with silencing; intergenic regions - usually methylated. Repetitive elements - usually methylated.
Why usually methylated? for genomic integrity - ensure no chromosomal changes occur in that region.
What is ICF syndrome? Immunodeficiency, Chromosomal instability and Facial anomolies syndrome - mutation in DNA methyltransferase 3b DNMT3B. Get hypomethylation of a small amount of the genome in patients.
What makes DNA methylation mitotically heritable? action of maintenance methyltransferase DNMT1.
What is the difference between passive demethylation and active? passive - lack of DNMT1, active - involves multiple steps and TET proteins.
Where do most histone tail modifications occur? on the N-terminal tails that protrude from the nucleosome, accessible to other chromatin proteins. More than 50 sites can be modified, but mostly on tails of H3 and H4.
Do all modifications have the same functions? No, different correlate to different functions. The functional outcomes of these various combinations is referred to as the "histone code". Could maybe map the histone code and infer outcomes based on histone marks.
What is histone acetylation correlated with? transcriptional activity, partly due to reduced positive charge of histones. Not mitotically heritable - not strictly epigenetic.
Does histone methylation alter the charge of the histone? no
Does histone methylation activate or inactivate? Activates H3K4me, inactivates H3K9me and H3K27me
Why do histone tail modifications correlate with different chromatin states? tail mods are read by other chromatin proteins. Consensus = specific histone mods don't cause altered gene expression, but may instead mark euk or hetero to aid in maintaining chromatin states.
Which modification is associated with euchromatin? H3K4 methylation and histone acetylation.
What is a common feature of the way long non-coding RNAs regulate epigenetic processes? formation of RNA-protein complexes that influence the regulation of gene expression.
What does sequence complementarity allow? the IncRNA to guide the epigenetic modifier complex to a specific location in the DNA.
How is X inactivation accomplished? via a prograssive accumulation of epigenetic marks on the inactive X chro.
What does inactive X chro have? Xist long noncoding RNA bound. Low levels of histone acetylation, accumulation of H3K27me and H3K9me, and DNA methylation of inactivated CpG islands.
What is the critical determinant for X inactivation? Xist. expressed from chro that will become inactive X. It coasts the the inactive X elect in cis.
What is Rett syndrome? x-linked neurodevelopmental syndrome - caused by mutation sin methyl binding domain protein MeCP2. Lethal in males before birth (hemizygous), heterozygous females survive. Phenotype is variable due to mosaicism.
What is skewing? equal chance of either X-chro being inactive, but can have up to 95% Xp silent, 5% Xm active or vice versa.
Created by: lmdavis97
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