CSB329H1 Lecture Notes - Lecture 2: Transferase, Insertional Mutagenesis, Demethylation
9 May 2018
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Lecture 2(b): Stem Cell Systems in Porifera and Cnidarins
Transposons & Transposon-Like Elements:
• Can make up to 50% of the eukaryotic mammalian genome (i.e. 44% in mice)
o Transposable elements are often quiescent, however, can be reactivated via DNA
demethylation
• Generally – unmethylated DNA is associated with active chromatin configuration and
methylated DNA is associated with inactive chromatin
o DNA methylation and demethylation play a critical role in germ line stem cells,
embryonic and adult somatic self-renewal, proliferation and differentiation
Worrisome…
• Transposons that are normally silent that can be reactivated via demethylation, this is worrying
because global demethylation occurs in mammals in two waves:
a. Shortly after fertilization and during the formation of primordial germ cells
b. Transposons that are highly methylated are prone to demethylation
ð This will expose the genome to the reactivation of transposons that can haul two different
regions of the genome
o Demethylation can promote aberrant expression and translocation of
transposons into different genes
§ Occasionally, this is a silent even; however, mutations can arise
ð Demethylation of transposons are potentially problematic as they can function as mutagens
o Can insert themselves into:
§ Introns and exons of functional genes and damage it
§ DNA flaking regions and alter or silencing gene expression
How Do we Silence Transposons?
• A way to silence transposons in germ line and somatic stem cells is to generate piRNAs and
synthesize companion PIWI protein family members
o Stem cells that are newly born express genes to produce proteins that are involved in
protecting the genome or involved in epigenetic reprogramming of cells as they are
going from germline status to a differentiated status
Activity of Transposons:
• Can move into regions of DNA with no sequence homology
• Can carry genes other types of genes; not only ones required for transposition
• Cause transposon insertional mutagenesis:
o Hemophilia A & B, Porphyria, Cancer
ð PIWI proteins function to repress “non-self” transposable elements
o How do they silence transposon translocation to target DNA?
ð There are different classes of transposons:
o Retrotransposons: RNA intermediate; reverse transcriptase to DNA & then insertion
o Inverted-Repeat Transposons: Transposase mRNA = transposase; excise & reinsert
Document Summary
Lecture 2(b): stem cell systems in porifera and cnidarins. This will expose the genome to the reactivation of transposons that can haul two different regions of the genome: demethylation can promote aberrant expression and translocation of transposons into different genes. Occasionally, this is a silent even; however, mutations can arise. Demethylation of transposons are potentially problematic as they can function as mutagens: can insert themselves into: Introns and exons of functional genes and damage it. Dna flaking regions and alter or silencing gene expression. Activity of transposons: can move into regions of dna with no sequence homology, can carry genes other types of genes; not only ones required for transposition, cause transposon insertional mutagenesis, hemophilia a & b, porphyria, cancer. There are different classes of transposons: retrotransposons: rna intermediate; reverse transcriptase to dna & then insertion, inverted-repeat transposons: transposase mrna = transposase; excise & reinsert.
