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SUMMARY:KRAB zinc fingers\, transposable elements and the evolution of gen
 e regulatory networks - Michael Imbeault (Department of Genetics\, Cambrid
 ge Univ)
DTSTART:20200211T150000Z
DTEND:20200211T160000Z
UID:TALK139630@talks.cam.ac.uk
CONTACT:Mateja Jamnik
DESCRIPTION:KRAB zinc finger proteins (KZFPs) are the largest subfamily of
  DNA binding factors in mammals. They emerged at the dawn of tetrapods and
  have since expanded at a dramatic pace\, with new members found at every 
 phylogenetic branch\; illustrative of that fact\, only 80 genes are shared
  between mouse and human out of their respective 350. They primarily targe
 t endogenous transposable elements and are involved in their transcription
 al control in embryonic stem cells through the recruitment of TRIM28 and t
 he subsequent deposition of repressive epigenetic marks (H3K9me3 and DNA m
 ethylation). KZFPs and transposable elements are thought to be locked in a
  fast-paced evolutionary arms race\, with new KZFPs continuously emerging 
 to tackle the genomic threat of invading transposable elements.\nInteresti
 ngly\, many KZFPs are targeting evolutionary conserved remains of transpos
 able elements\, millions of years after these have lost all replication po
 tential. Moreover\, these largely degraded transposable elements still con
 tain docking sites for transcription factors and are found to be epigeneti
 cally active in certain cellular contexts\; therefore\, they could partici
 pate in the rewiring of transcriptional networks by acting as enhancers or
  alternative promoters. Expression patterns of KZFPs are quite diverse and
  not restricted to embryonic stem cells\, hinting at roles outside the tra
 nscriptional repression of transposable elements during embryogenesis. We 
 are hypothesizing that one such role is to toggle accessibility of transpo
 sable element-derived enhancers\, resulting in the regulation of nearby ge
 nes in a cell-type specific fashion. \n\nIn this talk I will discuss the l
 atest developments emerging from my lab regarding this topic. We have proc
 essed large-scale genomic and transcriptomic datasets to generate high-res
 olution maps of the diversity of KZFP presence and activity between cell t
 ypes. This will be supplemented with a discussion of the fine-grained evol
 utionary history of KZFPs and their targets\, showcasing unsuspected patte
 rns of evolution in rodents. I will present some of our latest data from f
 unctional studies on a few specific KZFPs underlying important biological 
 processes such as immunity or development. Notably\, we have identified co
 mplex regulatory dynamics between KZFPs and their targets\, as well as cou
 nter examples to the arms race hypothesis. Overall\, our results improve o
 ur understanding of how KZFPs contribute to the evolution of gene regulato
 ry networks\, with implications for the interpretation of mutations found 
 within the non-coding genome.\n
LOCATION:FW26\, Computer Laboratory\, William Gates Builiding
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