HMB321H1 Lecture Notes - Lecture 15: Cpg Site, Histone Methylation, Methyl Group

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8 Oct 2011
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11 MAR 2011
HMB321 L15: Epigenetics in Cancer
Mechanisms of epigenetics
-Modifications are heritable, e.g. Imprinting -- without change to the DNA (just additive funct’al groups)
-Can include methylation, histone deacetylation, which interfere with transcription
DNA methylation
-Usually occur at the CpG island site (C-phosphate-G)
-CpG islands are high concentrations of CpG sequences; usually near gene promoters
-Lots of methylation can be incurred to turn genes off effectively
-Methylation at CpG => cytosine changes to 5-methylcytosine, which is not readable
-Process?
-Transcriptionally active chromatin => unmethylated; acetylated (allows euchromatin transcr)
-Transcriptionally competent chromatin => still transcribed because of acetylated, despite
methylation on gene
Histone acetylation
-Addition of acetyl group causes difference in transcriptional ability
-Deacetylation inactivates chromatin transcription (even more so with methylation)
-No deacetylation + methylation => still some transcription
Histone phosphorylation
-Ways to modify histone via addition of phosphate group to serine molecule
-Can reduce ability of histone to bind DNA to inhibit transcription
Histone methylation
-Addition of methyl to amino acids in R or K in histone tails (happens on actual protein)
-Alters the readability of the DNA bound by those histones
-May lead to activation or repression, depending on cellular context
4 Major histones
-H2A, H2B, H3, H4 are the 4 histones creating the nucleosome core that DNA wraps around
Imprinting (ref: L16, next week)
-Preferential expression of maternal or paternal allele
Bookmarking
-Method by which cells can replicate and pass along certain open/closed states of chromatin to transmit
the selective transcription of certain genes
-Important for cell specification (e.g. When cells for certain tissues are replication to form that tissue
type, they inherit a particular state of x genes to provide that specific tissue in y area)
Position effect variegation
-Alteration of gene expression that ensues after translocated to another region of a chromosome or
another chromosome
-E.g. Translocation of chr3 region (inactive) to chr17 => activates => transcribe genes in chr3
that were not readily transcribed on chr3, on chr17
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