CSB349H1 Lecture Notes - Lecture 7: Embryonic Stem Cell, Demethylation, Oct-4
14 May 2018
School
Department
Course
Professor
Lecture 7(a): Methylation Dynamics & Monoallelic Expression
DNA Methylation & Development:
• Dynamic regulation of methylation is crucial during early development is accomplished by
de novo methyltransferases (Dnmt3a/b)
ð Epigenetic memory – DNA methylation is inherited across generations:
o During development, the DNA methylation that occurs is
erased twice
and then later
reintroduced gradually through development
§ Epigenetic memory allows for the precise organized manner of when, where,
and how DNA methylations are introduced – it is not random
Early Mammalian Development:
• Fertilization will lead to forming a zygote
o Zygote will begin to divide and
after 4 days we will reach the
blastocyst stage
• Blastocyst consists of an inner cell mass which are pluripotent embryonic stem cells
o ICM => pluripotent cells capable of forming all three germ layers of the embryo
o Trophectoderm => multipotent cells capable of forming extra embryonic tissue
• After zygote formation all DNA methylation is erased – embryonic stem cells have the lowest
level of DNA methylation
o OCT4 and NANOG are transcription factors that regulate pluripotency in ESCs
§ ESCs have unique epigenetic signature:
• OCT4 & NANOG promotors contain CpGs that are
hypomethylated in ESCs
• CpGs become hypermethylated as ESCs undergo differentiation
ð Methylation status change dramatically during the differentiation of ESCs into a tissue-specific
stem cell; from hypomethylation to hypermethylation
ð The epigenetic (methylation) status of a cell is a strong indicator of its past and present
developmental state – it provides indications about its future potential
Document Summary
Dna methylation & development: dynamic regulation of methylation is crucial during early development is accomplished by de novo methyltransferases (dnmt3a/b) Epigenetic memory dna methylation is inherited across generations: during development, the dna methylation that occurs is erased twice and then later reintroduced gradually through development. Epigenetic memory allows for the precise organized manner of when, where, and how dna methylations are introduced it is not random. Escs have unique epigenetic signature: oct4 & nanog promotors contain cpgs that are hypomethylated in escs, cpgs become hypermethylated as escs undergo differentiation. Methylation status change dramatically during the differentiation of escs into a tissue-specific stem cell; from hypomethylation to hypermethylation. The epigenetic (methylation) status of a cell is a strong indicator of its past and present developmental state it provides indications about its future potential. Actively demethylated: maternal dna (red line) Imprinted genes (green line: both maternal and paternal genes that do not undergo demethylation.
