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Enhancers and Insulators

Enhancers and Insulators. Overview: chromosomal looping is required for enhancer action Insulators can block Enhancers Enhancer models. SHH Sonic Hedgehog. Example today:. MFCS1. Greek mythology and sonic hedgehog signaling: holoprosencephaly.

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Enhancers and Insulators

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  1. Enhancers and Insulators Overview: chromosomal looping is required for enhancer action Insulators can block Enhancers Enhancer models

  2. SHH Sonic Hedgehog Example today: MFCS1

  3. Greek mythology and sonic hedgehog signaling: holoprosencephaly

  4. An distant enhancer controls limb development

  5. The sonic hedgehog (shh) enhancer shh enhancer: MFCS1 shh probe enhancer probe FISH Probes

  6. FISH: Fluorescent in situ hybridization

  7. The sonic hedgehog (shh) enhancer shh enhancer: MFCS1 shh probe enhancer probe FISH Probes

  8. SHH enhancer comes physically close to the shh locus in cells were shh is actively transcribed shh active shh inactive shh probe enhancer probe

  9. Chromosome Conformation Capture confirms looping model

  10. 3C shows that shh enhancer comes physically close to shh locus

  11. Enhancers pose two specific problems How can Enhancers function over great distances? some enhancers regulate gene expression despite being hundreds of thousands base pairs away How can Enhancers be restricted to specific genes? if enhancers can reach out over large distances, how come they only regulate some of the genes within their range?

  12. Gene B Gene A enhancer How do enhancers choose the right gene? Since enhancers function over huge distances, they could potentially (mis-) regulate many genes.

  13. Mechanisms of regulating enhancer-promoter specificity

  14. Fushi tarazu expression in Drosophila embryos

  15. Why do Scr and ftz have different patterns? Scr : Sex combs reduced (encodes homeodomain transcription factor) ftz: fushi tarazu (also encodes homeodomain transcription factor)

  16. The AE-1 enhancer works with TATA and DPE promoters

  17. The AE-1 enhancer preferentially activates TATA promoters

  18. Enhancer models

  19. Promoter-centered interactions Transcription factories (red spots) Nucleus in human cell Multi-gene interaction Complex (“chroperon”)

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