Understanding the regulation of Polycomb Repressor Complex 1 and its role in epigenetic control of gene expression

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Cells, the basic unit of all mammals, contain all the information for cell survival and proliferation, which are highly regulated processes. One regulatory mechanism is the expression of specific proteins. Different proteins are encoded from unique DNA sequences known as genes. DNA is packaged into chromatin using a complex made up of histones, providing a further level of regulation on top of DNA sequence. Chromatin can be modified to regulate gene expression and therefore protein levels in the cell. One complex of proteins that is known to modify chromatin is called the polycomb complex PRC1. PRC1 is able to modify a histone and this is associated with gene repression. The PRC1 complex has been shown to play an important role in cell survival and proliferation, through its ability to modify chromatin. How the PRC1 complex is regulated and how it is able to recognise chromatin to modify it is poorly understood. The work described in this proposal is aimed at elucidating how PRC1 is regulated and in turn how this regulates gene expression to maintain healthy cells.
 
Description We showed how a key protein complex PRC1 is recruited to chromatin to regulate how the chromatin is organised to regulate gene expression in embryonic stem cells we have shown how this complex is regulated by signalling pathways from environmental cues.
Exploitation Route these are basic mechanistic finding of how a key protein complex functions, this complex is miss-regulated during development, in ageing and in multiple cancers. Our data can be utilised by other who will use these finding to potentially develop stem cell therapies, and drug treatments.
Sectors Education,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Title promoter capture Hi-C 
Description It contains genome wide chromatin interactions from mouse embryonic stem cells 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact This will provide a resource for other members of the scientific community 
 
Description Role of Polycomb repressive complexes in nuclear organisation 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided promoter capture Hi-C Next sequencing data
Collaborator Contribution Our collaborator has analysed our Hi-C next generation sequencing data
Impact This work will be published in a peer review journal. This is multi-disciplinary and involved Stem cell research and bioinformatics
Start Year 2011
 
Description Understanding recruitment of Polycomb repressive complexes 
Organisation University of Oxford
Department Department of Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Research results based on mass spectrometry
Collaborator Contribution Research results on ChIP-seq
Impact doi: 10.1016/j.celrep.2014.04.012 doi: 10.1016/j.cell.2011.12.029
Start Year 2010
 
Description Functional role of PRC1 recruitment in embryonic stem cells 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact presented a poster at a scientific conference and stimulated discussions with other scientific researchers

NA
Year(s) Of Engagement Activity 2012
 
Description Schools day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact School children were engaged in science

Members of the group reported back that the project was excellent and that it had made them very interested in research biology
Year(s) Of Engagement Activity 2010,2011,2012,2014
 
Description visit to special needs school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Gave a talk to a class of children with learning difficulties on the fun aspects of science

After my talk the children were engaged in science activities more.
Year(s) Of Engagement Activity 2012