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Self-Perpetuating Structural States in Biology, Disease, and Genetics (2002) / Chapter Skim
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The insulation of genes from external enhancers and silencing chromatin
Pages 57-61

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From page 57...
... The possibilities thus arise that the active gene will be inappropriately silenced by the condensed chromatin or will inappropriately activate the adjacent silent gene. It is equally possible that in other tissues or at other developmental stages, where this gene is inactive, signals from adjacent extraneous enhancers could cause incorrect patterns of expression.
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From page 58...
... These results indicate that CTCF plays Enhancer an important role as an insulator protein in allele-specific B' k regulation at this imprinted locus, and that the insulator function OC Ing can be modulated by DNA methylation, thus making the CTCF sites susceptible to epigenetic regulation. Quite recently a cluster of differentially methylated CTCF sites has been identified at the Xist gene promoter, and it has been suggested that these are enhancer-blocking elements important for X chromosome inactivation (13~.
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From page 59...
... At all stages, the approximately 16-kb condensed chromatin region upstream of the globin genes remains unacetylated. Furthermore, there is a peak of acetylation over the 5'HS4 insulator element (as well as over the HSA enhancer of the FR gene)
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From page 60...
... A related mechanism has been proposed for barrier activity in Saccharomyces cerevisiae, where a site that binds histone acetylases is sufficient to prevent extension of silencing from HMR-E (21~. These results suggest that in vivo the 5'HS4 insulator has two functions: it serves as an enhancer blocking element to screen out upstream signals, and it also acts as a barrier against the advance of the condensed chromatin structure immediately upstream.
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From page 61...
... We note that the CTCF site at the 3' end of the globin locus is not accompanied by the other subregions present in 5'HS4 and is also not a site of strong acetylation. The condensed chromatin at the 3' end of the locus is facilitative, i.e., it must open for expression of the odorant receptor, and it may therefore be distinct in properties from the constitutive condensed chromatin at the 5' end and may not require an acetylated barrier.
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Key Terms

  • condensed chromatin
  • blocking activity
  • barrier function
  • position effects
  • chromatin region

  • ctcf sites
  • histone acetylation
  • ctcf site
  • transmitted allele
  • globin genes

  • imprinted locus
  • odorant receptor
  • reporter expressing
  • measure protection
  • globin chromatin

  • chromatin structure
  • downstream endodermal
  • called insulators
  • chromatin domain
  • regulatory elements

  • ctcf binding
  • folate receptor
  • elements called
  • allele expresses
  • strong enhancer

  • binding sites
  • mating type
  • type locus
  • histone methylation
  • sequence elements


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