text: The first examples of insulators in vertebrates was seen in the chicken β-globin locus, cHS4. cHS4 marks the border between the active euchromatin in the β-globin locus and the upstream heterochromatin region that is highly condensed and inactive. The cHS4 insulator acts as both a barrier to chromatin-mediated silencing via heterochromatin spreading, and blocks interactions between enhancers and promoters. A distinguishing characteristic of cHS4 is that it has a repetitive heterochromatic region on its 5' end.
  The human β-globin locus homologue of cHS4 is HS5. Different from the chicken β-globin locus, the human β-globin locus has an open chromatin structure and is not flanked by a 5 heterochromatic region. HS5 is thought to be a genetic insulator in vivo' as it has both enhancer-blocking activity and transgene barrier activities.
  CTCF was first characterized for its role in regulating β-globin gene expression. At this locus, CTCF functions as an insulator-binding protein forming a chromosomal boundary. CTCF is present in both the chicken β-globin locus and human β-globin locus.  Within cHS4 of the chicken β-globin locus, CTCF binds to a region (FII) that is responsible for enhancer blocking activity.