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Mapping the retrotransposon-mediated layer of neuronal gene regulation in the human genome

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EC-Contrib. €

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Project "PRIMATE-TE-IMPACT" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT VAN AMSTERDAM 

Organization address
address: SPUI 21
city: AMSTERDAM
postcode: 1012WX
website: www.uva.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country Netherlands [NL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-08-01   to  2022-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT VAN AMSTERDAM NL (AMSTERDAM) coordinator 1˙500˙000.00

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 Project objective

Throughout evolution, the human genome has been attacked by retrotransposons, parasitic DNA elements that spread through our genome by a copy-paste activity. I previously showed that SVA elements, the youngest class of retrotransposons in our genome, harbour a strong gene-regulatory potential which is normally repressed by KRAB zinc finger protein ZNF91 (Jacobs et al., 2014, Nature). However, for reasons unknown, repression of retrotransposons is much less efficient in the human brain, resulting in activation of the enhancer potential of SVA elements spread throughout the human genome. The importance of these SVA insertions for the evolution of human neuronal gene-regulatory networks, and how many genes have come to depend on SVA's regulatory influence, remains elusive. In this research program, I will use ‘cortical organoids’; three-dimensional brain tissues derived from human and primate stem cells, to investigate how recent SVA insertions have impacted human neuronal gene expression. Furthermore, I will investigate how changes of the epigenetic landscape in neurons affect the activity of retrotransposons in our genome and the influence they have on nearby neuronal genes. Finally, I will explore the possibility that loss of epigenetic silencing of retrotransposons is responsible for dysregulation of genes associated with neurological diseases. Preliminary findings suggest a potential role for retrotransposons in susceptibility loci for Alzheimer's and Parkinson's disease. Finding further support for this in the current research program, will form the basis of a novel concept which explains how changes in the epigenetic landscape can uncover a dormant genetic predisposition to disease.

 Publications

year authors and title journal last update
List of publications.
2020 Grace Farmiloe, Gerrald A. Lodewijk, Stijn F. Robben, Elisabeth J. van Bree, Frank M. J. Jacobs
Widespread correlation of KRAB zinc finger protein binding with brain-developmental gene expression patterns
published pages: 20190333, ISSN: 0962-8436, DOI: 10.1098/rstb.2019.0333
Philosophical Transactions of the Royal Society B: Biological Sciences 375/1795 2020-04-03
2019 Nilda Vanesa Ayala-Nunez, Gautier Follain, François Delalande, Aurélie Hirschler, Emma Partiot, Gillian L. Hale, Brigid C. Bollweg, Judith Roels, Maxime Chazal, Florian Bakoa, Margot Carocci, Sandrine Bourdoulous, Orestis Faklaris, Sherif R. Zaki, Anita Eckly, Béatrice Uring-Lambert, Frédéric Doussau, Sarah Cianferani, Christine Carapito, Frank M. J. Jacobs, Nolwenn Jouvenet, Jacky G. Goetz,
Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-12408-x
Nature Communications 10/1 2020-04-03
2018 Ian T. Fiddes, Gerrald A. Lodewijk, Meghan Mooring, Colleen M. Bosworth, Adam D. Ewing, Gary L. Mantalas, Adam M. Novak, Anouk van den Bout, Alex Bishara, Jimi L. Rosenkrantz, Ryan Lorig-Roach, Andrew R. Field, Maximilian Haeussler, Lotte Russo, Aparna Bhaduri, Tomasz J. Nowakowski, Alex A. Pollen, Max L. Dougherty, Xander Nuttle, Marie-Claude Addor, Simon Zwolinski, Sol Katzman, Arnold Kriegstein, Evan E. Eichler, Sofie R. Salama, Frank M.J. Jacobs, David Haussler
Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis
published pages: 1356-1369.e22, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.03.051
Cell 173/6 2019-04-16
2018 Diana Pereira Fernandes, Mainá Bitar, Frank Jacobs, Guy Barry
Long Non-Coding RNAs in Neuronal Aging
published pages: 12, ISSN: 2311-553X, DOI: 10.3390/ncrna4020012
Non-Coding RNA 4/2 2019-04-16

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