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CATEGORIES:Babraham Seminar
SUMMARY:Genetic features controlling the specific expressi
 on of developmental genes - Dr Alvaro Rada-Iglesia
 s\; Institute of Biomedicine and Biotechnology of 
 Cantabria
DTSTART;TZID=Europe/London:20230426T133000
DTEND;TZID=Europe/London:20230426T143000
UID:TALK197833AThttp://talks.cam.ac.uk
URL:http://talks.cam.ac.uk/talk/index/197833
DESCRIPTION:During vertebrate embryogenesis\, developmental ge
 nes are expressed with remarkable specificity (i.e
 . expression of the correct genes in the correct c
 ell types) and spatio-temporal precision (i.e. low
  transcriptional variation within a field of cells
 ). It is widely accepted that the establishment of
  cell-type specific gene expression programs is la
 rgely dependent on the regulatory activity of enha
 ncers. However\, the mechanisms that enable enhanc
 ers to induce their target genes with the required
  precision and specificity are still poorly unders
 tood. Using a synthetic engineering approach\, we 
 recently showed that enhancer-associated CpG islan
 ds (CGI) act as tethering elements that increase t
 he physical and functional communication between d
 istal enhancers and their target genes\, particula
 rly those with large CGI clusters in their promote
 rs (i.e. developmental genes). Moreover\, using si
 ngle-cell measurements\, we also uncovered that CG
 I contribute to the precise induction of developme
 ntal genes by increasing transcriptional burst siz
 e and frequency. On the other hand\, we noticed th
 at developmental genes tend to be located close to
  TAD boundaries\, while their cognate enhancers ha
 ve a more random distribution within TADs. Notably
 \, to interrogate whether the positioning of devel
 opmental genes within TADs has any functional rele
 vance\, we generated various genetic rearrangement
 s in two selected loci (i.e. Gbx2/Asb18\; Six3/Six
 2). Interestingly\, these experiments revealed tha
 t the presence of CTCF site clusters\, and develop
 mental genes close to TAD boundaries synergistical
 ly strengthens transcriptional insulation and prev
 ents enhancers from activating non-target genes. O
 verall\, our findings provide novel insights into 
 the mechanisms controlling transcriptional precisi
 on and specificity during development\, which\, in
  turn\, can also help us to understand and predict
  the long-range pathological effects of human stru
 ctural variation.\n\nAlvaro Rada Iglesias received
  his M.Sc. in Biology by the University of Leon in
  2001\, being recognized as the best academic curr
 iculum of that year. Then\, he obtained his PhD in
  2007 at Uppsala University (Sweden)\, where he wo
 rked in the laboratory of Prof. Claes Wadelius. Af
 ter a short post-doctoral work in the Linnaeaus Ce
 ntre for Bioinformatics (Uppsala University\, Swed
 en) under the supervision of Prof. Jan Komorowski\
 , he obtained an EMBO long-term fellowship to cont
 inue his postdoctoral career in the laboratory of 
 Prof. Joanna Wysocka at Stanford University (USA)\
 , where he stayed between 2009-2013. In 2013\, he 
 was recruited by the University of Cologne as a Ju
 nior Research Group Leader at the Centre for Molec
 ular Medicine Cologne\, where he successfully star
 ted his independent research group. This was recog
 nized with an EMBO Young Investigator award (EMBO 
 YIP) in 2017. In July 2018 he was recruited as a P
 rincipal Investigator by the University of Cantabr
 ia to direct his research group at the Institute o
 f Biomedicine and Biotechnology of Cantabria (IBBT
 EC).  In 2020\, he became a Tenured Scientist at t
 he Consejo Superior de Investigaciones Científicas
  (CSIC). In recent years\, his work has been recog
 nized by an EMBO Young Investigator award (EMBO YI
 P\; 2017)\, the José Luís Gómez Skarmeta award (20
 20) and an ERC Consolidator grant (2019).
LOCATION:Kings Hedges Room 
CONTACT:Bobbie Claxton
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