Non-coding RNAs and transcription as epigenetic regulators
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
Abstract
Transcription and ncRNAs are major modifiers of the epigenetic state, but the mechanisms by which they act are still poorly understood. In this Theme, we investigate the role of ncRNAs, initially using a yeast model system, (1) in genome stability, (2) their influence on meiotic recombination, (3) the role of antisense ncRNAs in chromatin structure modulation, and in mice (4) how transcription promotes DNA methylation at imprinted loci.
Organisations
Publications
Cruz C
(2014)
Endogenous RNA interference is driven by copy number.
in eLife
De La Rica L
(2016)
TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells.
in Genome biology
Donà F
(2014)
Unexpected DNA loss mediated by the DNA binding activity of ribonuclease A.
in PloS one
Frenk S
(2014)
The nuclear exosome is active and important during budding yeast meiosis.
in PloS one
Frenk S
(2017)
Aging yeast gain a competitive advantage on non-optimal carbon sources.
in Aging cell
Gahurova L
(2017)
Transcription and chromatin determinants of de novo DNA methylation timing in oocytes.
in Epigenetics & chromatin
Houseley J
(2015)
Annual meeting of the EpiGeneSys Network of Excellence--Advancing epigenetics towards systems biology.
in BioEssays : news and reviews in molecular, cellular and developmental biology
Jack CV
(2015)
Regulation of ribosomal DNA amplification by the TOR pathway.
in Proceedings of the National Academy of Sciences of the United States of America
Makovets, Svetlana
(2013)
DNA Electrophoresis: Methods and Protocols
Selleri L
(2016)
A Hox-Embedded Long Noncoding RNA: Is It All Hot Air?
in PLoS genetics
| Description | Transcription and non-coding RNAs are major modifiers of the epigenetic state, but the mechanisms by which they act are still poorly understood. In the oocyte system, we showed how gene transcription confers different layers of epigenetic marks by remodelling histones to direct DNA methylation. We have subsequently been able to show that transcriptional differences, for example that relate to how oocytes are sourced for assisted reproduction technologies, are associated with predictable differences in DNA methylation.In yeast, we characterised the interplay between transcription and genetic change, showing that cells are able to remodel specific regions of their genomes in response to environmental conditions, based on the transcriptional changes induced by those environments. We further elucidated the manner in which genetic changes, particularly in DNA copy number, influence RNA processing, showing that complex feedback relationships exist between the genome and the transcriptome. These findings have underpinned more work in the following Epigenetics ISP characterising the changes in the genome and epigenome that occur during ageing in yeast and how these impact the ageing process. |
| Exploitation Route | This is all covered in other entries |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.babraham.ac.uk/our-research/epigenetics |
| Description | As part of the wider Babraham Institute strategy, across the course of this ISP we have developed a much broader public engagement strategy, undertaking large prestigious events including two Royal Society exhibits specifically showcasing our work (Epigenetics: DNA is not your destiny and Race Against the Ageing Clock), as well as presentations at local science fairs and engagement with local schools. We have also contributed substantially to transferable skills development, analytical thinking and training, mentoring and career development. |
| First Year Of Impact | 2014 |
| Sector | Healthcare |
| Impact Types | Societal,Economic |
| Description | Babraham Institute Public Dialogue 2015 |
| Geographic Reach | National |
| Policy Influence Type | Citation in other policy documents |
| Impact | Improved public understanding of biological sciences and the work of the Babraham Institute |
| URL | http://www.babraham.ac.uk/get-involved/partnerships-page/public-dialogue |
| Description | Chair SAB Development and Genetics Unit Institut Curie |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Participation in a advisory committee |
| Impact | Probably the best unit of this type in France |
| Description | H2020 EU-LIFE project "LIBRA", co-lead work package "Gender Equality in Research" |
| Geographic Reach | Europe |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Consideration of gender effects in research, appreciation that there may be sex differences in cell lines, animal models and treatment regimes that ought to be taken into consideration when designing studies. |
| Description | EU BLUEPRINT |
| Amount | £500,000 (GBP) |
| Funding ID | 282510 |
| Organisation | European Commission |
| Department | Seventh Framework Programme (FP7) |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | EU NoE EpiGeneSys |
| Amount | £400,000 (GBP) |
| Funding ID | 257082 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | Senior Research Fellowship |
| Amount | £1,426,775 (GBP) |
| Funding ID | 110216/Z/15/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2016 |
| End | 03/2021 |
| Title | DMDD |
| Description | As part of the Wellcome Trust funded Strategic Award "Deciphering the Mechanisms of Developmental Diseases", we have generated a database in which we collect phenoytping data of the mouse placenta at various gestational stages. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | Broad survey of embryonic lethal gene mutations for defects in embryonic and placental development. Efforts will lead, for the first time, to a global overview of the number and identity of genes, and the molecular pathways they regulate, involved in the development of the placenta as an essential organ ensuring reproductive success and health of the baby. |
| URL | http://www.nimr.mrc.ac.uk/news/deciphering-the-mechanisms-of-developmental-disorders-progress-report... |
| Title | Yeast gene expression in meiosis |
| Description | Gene expression in meiosis of wt and trf4 mutant yeast |
| Type Of Material | Database/Collection of data |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | data re-use |
| URL | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60221 |
| Description | Analysis of histone modifications in mice with loss-of-imprinting of Zac1 |
| Organisation | Clermont Université |
| Country | France |
| Sector | Academic/University |
| PI Contribution | Our group was responsible for framing the project and experimental design; we provided tissues from mice with loss-of-imprinting of Zac1. |
| Collaborator Contribution | Their group performed ChIP-PCR analysis in tissues from Zac1 loss-of-imprinting mice we provided. |
| Impact | Joint publication Veselovska et al. 2015 Genome Biol. |
| Start Year | 2013 |
| Description | Antisense-mediated promoter silencing in imprinted locus Gnas |
| Organisation | MRC Harwell |
| Department | MRC Mammalian Genetics Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Our team provided a gene targeting construct for one of the targeting alleles used by the partner, which complemented work we previously published in Chotalia et al. 2009 Genes & Dev. |
| Collaborator Contribution | Their team was responsible for framing the project and experimental design and data analysis. |
| Impact | Joint publications Williamson et al. PLoS Genet. 2011; Tibbit et al., 2015 Non-coding RNA |
| Start Year | 2007 |
| Description | Human Cell Atlas |
| Organisation | Broad Institute |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | Contributed to formulating the white paper of the Human Cell Atlas. |
| Collaborator Contribution | Conceived the project and brought the international consortium together. |
| Impact | The white paper was published Regev et al 2017. It involves single cell biologists and computational and modelling scientists. |
| Start Year | 2016 |
| Description | MR for CJ paper |
| Organisation | University of Cambridge |
| Department | Cambridge Systems Biology Centre (CSBC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We performed mechanistic analysis of rDNA CNV |
| Collaborator Contribution | Markus Ralser's group performed metabolomics analysis |
| Impact | Jack et al PNAS paper |
| Start Year | 2013 |
| Description | Miguel Branco for TET paper |
| Organisation | Queen Mary University of London |
| Department | Blizard Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | RNA analysis of L1 trasposon |
| Collaborator Contribution | This project was run by the Branco lab, they produced the bulk of the data and published the paper. |
| Impact | Research publication PMID 27863519 |
| Start Year | 2015 |
| Title | AGENT TO PREVENT THE EMERGENCE OF RESISTANCE TO A THERAPEUTIC AGENT |
| Description | The invention relates to the use of a histone acetyltransferase inhibitor to prevent the emergence of mutations causing resistance to a therapeutic agent. The invention also relates to the use of an mTOR inhibitor to prevent the emergence of mutations causing resistance to a therapeutic agent. The invention also relates to novel pharmaceutical compositions comprising a histone acetyltransferase inhibitor or an mTOR inhibitor in combination with a therapeutic agent and to the uses of said compositions in the treatment of disease, such as cancer. |
| IP Reference | WO2017085473 |
| Protection | Patent application published |
| Year Protection Granted | 2017 |
| Licensed | No |
| Impact | Used to leverage contacts with biotech industry, notably within Astra Zeneca. |
| Description | Article on JH lab Ageing Research in Cambridge Independent |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | An article on our yeast research was published following an in depth interview with me (JH). |
| Year(s) Of Engagement Activity | 2017 |
| Description | Babraham Schools Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | As part of the annual Babraham Schools' Day, my group hosted 5 GCSE and 5 A level students for half-day practical sessions in the lab. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Cambridge Science Festival: Molecular Explorers, Cambridge (UK) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Exhibit at Cambridge Science Festival, engaging with visitors at stall explaining the science and advances made in the area, answering questions and discussing outstanding research goals |
| Year(s) Of Engagement Activity | 2017 |
| Description | Poster at Ageing meeting |
| 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 | General interest in presented work. networking |
| Year(s) Of Engagement Activity | 2014 |
| Description | Poster at EMBO transcription meeting |
| 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 | General interest in presented work. Presentation by my student, he successfully approached future employers. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Royal Society Partnering Award - CS + LW, NM, SC |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Successful application for Royal Society Partnering Award. Poster 6 selected 6th form students over the course of 1 week and conducted in-depth research project. Data analysis followed at the pupils' school directly. |
| Year(s) Of Engagement Activity | 2016,2017 |
| Description | STEM teacher visit |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | As part of a week-long visit to the Institute, my group hosted 3 biology A-level teachers from local schools for involvement in practical work in the lab over a 2-day period. |
| Year(s) Of Engagement Activity | 2016 |
| 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 | Groups of 5-6 6th-form students take part in a one-day visit to 2 research groups at the Babraham Institute and conduct two small research experiments during that day. |
| Year(s) Of Engagement Activity | 2017,2018 |
| 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 | Local |
| Primary Audience | Schools |
| Results and Impact | Project design, scientific background induction and practical supervision for 6th form students as well as teachers during Annual Schools Day. |
| Year(s) Of Engagement Activity | 2015,2016,2017 |
| Description | Schools day (annual) |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Visit by school children to do experiments in BI labs. All BI labs participate. |
| Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014,2015,2016 |
| Description | Talk and poster at EMBO Evolution meeting |
| 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 | General interest in presented work. networking |
| Year(s) Of Engagement Activity | 2014 |
| Description | Talk at DNA Replication as a Source of DNA Damage Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk to other members of research community. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.fusion-conferences.com/conference67.php |
| Description | Talk at EMBO non-coding RNA meeting |
| 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 | General interest in presented work. networking |
| Year(s) Of Engagement Activity | 2014 |
| Description | Talk at Epigenesys meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation at Epigenesys meeting |
| Year(s) Of Engagement Activity | 2016 |
| Description | Talk at UK RNA meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Conference presentation |
| Year(s) Of Engagement Activity | 2016 |
| Description | Talk at UK Yeast meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | General interest in presented work, invitations for further talks. networking |
| Year(s) Of Engagement Activity | 2012 |
| Description | Talk at University of Edinburgh |
| 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 | Seminar and conference presentation networking |
| Year(s) Of Engagement Activity | 2013 |
| Description | Talk at University of Manchester |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Invited Seminar at Faculty of Biology Networking |
| Year(s) Of Engagement Activity | 2013 |