Lecture 7 "Our genome strikes back: The evolutionary arms race between KRAB zinc finger genes and transposable elements''

Question 1

Expansion of KRAB Zinc Finger genes

Answer 1

they are transcriptional repressors, KRAB-ZNF clusters have greatly expanded in higher vertebrates and Primates in particular, KRAB ZNF regions are loaded with signals of positive selection.

Question 2

What is the purpose of having many Zinc Fingers?

Answer 2

ZNF are protecting against retroviral DNA insertions. So they work as a genome defense mechanism against retrotransposons invasions.

Question 3

Zinc Fingers

Answer 3

ZNFs are recognizing three nucleotides, mutiple ZNFs togheter recognise a sequence. ZNFs are working as a defense mechanism against active retrotransposons by respressing this. KRAB ZNF recruit KRAB associated protein 1 (KAP1) to exert their repressive actions.
KO of KAP1 leads to re-expression of retro gene

Question 4

Are KRAB ZNFs part of a species-specific defense mechanism against retrotransposon invasions?

Answer 4

They did an experiment to prove this with a mouse cell where they insert a human chromosome. They looked if the retrotransposon was silenced or not by KAP1, and it did not. So SVA and L1 retrotransposons are deregulated in a non-primate cellular background.

Question 5

ZNF91

Answer 5

Repressors of SVAs
They found this by testing all potential ZNFs one by one with a luciferase sequence after the SVA

Question 6

ZNF93

Answer 6

Repressors of L1
because of an evolutionary change there is an part of the ZNF93 recognise sequence deleted, this is an mechanisms of the retrotransposon to escape. Loss of ZNF93 binding site sparked a new invasion of L1! The ZNF93 needs to evolve to be able to bind to L1 again.
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