Epigenome

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Epigenome

• 12-4-06

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Pikaard CS. The epigenetics of nucleolar
dominance. Trends Genet. 2000 16(11)495-500.
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Lawrence RJ, et al. Mol Cell. 2004 13(4)599-609.
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Mechanisms of chromatin based regulation
Chromatin assembly factors Structural components
of chromatin
Encoding activities - Histone tail
modifications - DNA modifications
Strahl and Allis, Nature 2000
Decoding of chromatin information - Reading DNA
modification patterns - Reading histone
modification patterns
Physical remodeling of chromatin - SWI/SNF
complexes
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Outline

• Histone variants/turnover
• Histone modifications
• Effects of histone modifications
• Chromatin remodeling

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Histone variants and replacement

• One way to vary chromatin is to use specific
  histone variants
• This requires specialized assembly or replacement
  processes
• A whole field of study involving the machinery
  for chromatin assembly and the histone specificity

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Henikoff S, Ahmad K. Assembly of Variant
Histones into Chromatin. Annu Rev Cell Dev Biol.
2005
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Histones and the nucleasome
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Histone code hypothesis

• Eukaryotic gene expression states are controlled
  by the post-translation modifications of histone
  tails
• Requires systems to modify and interpret
  modifications

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Histone methylation

• The SET domain was identified as a conserved
  region present in three Drosophila proteins
  required for epigenetic regulation Su(var)3-9,
  E(z) and TRX
• The SET domain is well conserved in many plant
  and animal proteins
• Recently, numerous studies have found that the
  SET domain is capable of histone
  methyltransferase activity
• Different SET domain proteins show differing
  substrate specificity
• Histone methylation can be a mark of either
  active or inactive chromatin

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Affects of histone modification

• Direct
• Indirect
• Memory?

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Stability of histone methylation
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Interaction between DNA and histone methylation
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Summary points

• Chromatin is a dynamic structure with numerous
  informational inputs
• Histone variants may play role
• Histone modifications can play a role
  individually or combinatorially
• Histone modifications have both direct and
  indirect affects
• Most modifications set up self-reinforcing loops

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Liu CL, Kaplan T, Kim M, Buratowski S, Schreiber
SL, Friedman N, Rando OJ. Single-nucleosome
mapping of histone modifications in S.
cerevisiae. PLoS Biol. 2005 3(10)e328
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Control of DNA methylation patterns

• Where is DNA methylation located in the genome?
• Techniques for studying DNA methylation
• 5meC antibody
• Restriction isoschizmers
• McrBC
• MBD domains
• RIPing in Neurospora
• DNA methylation in plant and animal genomes

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• Repeat induced point mutation
• Occurs in Neurospora, which has almost no gene
  duplications
• Any duplicated sequence over 400bp in length
  gets GC to AT mutations after meiosis
• Remaining CG sequences are heavily methylated

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Zhang X, et al. Genome-wide high-resolution
mapping and functional analysis of DNA
methylation in arabidopsis. Cell. 2006
126(6)1189-201.
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Affects of DNA methylation on gene expression
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Affects of DNA methylation on antisense expression
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Genes regulated by DNA methylation
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ncRNAs regulated by DNA methylation
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