“We are interested in how genomic and epigenetic information is integrated with extrinsic signals to promote concerted changes in gene expression”.
We aim to decipher the ground rules of gene regulation and establish their functional interplay in biological phenomena involving global changes in phenotype, such as in cell differentiation and activation. Our current focus is on the role of non-coding DNA elements such as enhancers in integrating and transmitting gene regulatory information.
We combine experimental and computational approaches to study these questions, capitalising on our previous work on promoter-enhancer relationships, organisation of DNA regulatory elements and population genomics. Our particular interest is in human primary cells as models, and in genetic and epigenetic variation as “natural perturbations” in the system.
Our ultimate goal is to generate comprehensive functional models of gene control “logic” underlying cellular decisions. Interrogation and validation of these models will pinpoint key individual players (regulatory elements, genes, extrinsic signals) and their regulatory relationships in these processes and shed light on how they are remodelled in disease.
Freire-Pritchett P* / Schoenfelder S*, Várnai C, Wingett SW, Cairns J, Collier AJ, García-Vílchez R, Furlan-Magaril M, Osborne CS, Fraser P, Rugg-Gunn PJ^, Spivakov M^. (2017). Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells. eLife, 6. doi: 10.7554/eLife.21926.
* joint first authors, ^ joint corresponding authors.
Javierre B-M* / Burren OS* / Wilder SP* / Kreuzhuber R* / Hill SM*, Sewitz S, Cairns J, Wingett SW, Várnai C, Thiecke MJ, Burden F, Farrow S, Cutler AJ, Rehnström K, Downes K, Grassi L, Kostadima M, Freire-Pritchett P, Wang F, The BLUEPRINT Consortium , Stunnenberg HG, Todd JA, Zerbino DR, Stegle O, Ouwehand WH, Frontini M^ / Wallace C^ / Spivakov M^# / Fraser P^. (2016). Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters Cell, 167(5), 1369-1384.
Cairns J* / Freire-Pritchett P*, Wingett SW, Várnai C, Dimond A, Plagnol V, Zerbino D, Schoenfelder S, Javierre B-M, Osborne C, Fraser P, Spivakov M. (2016). CHiCAGO: Robust Detection of DNA Looping Interactions in Capture Hi-C data. Genome Biology, 17(1), 127. PMID: 27306882.
F1000 Prime recommended paper. * joint first authors.
Bolland DJ* / Koohy H*, Wood AL, Matheson LS, Krueger F, Stubbington MJT, Baizan-Edge A, Chovanec P, Stubbs BA, Tabbada K, Andrews SR, Spivakov M^, Corcoran AE^. (2016). Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination. Cell Reports, 15(11), 2475–2487. PMID: 27264181.
F1000 Prime recommended paper. * joint first authors; ^ joint corresponding authors.
Spivakov M. (2014). Spurious transcription factor binding: Non-functional or genetically redundant? BioEssays, 36(8), 798-806. PMID: 24888900.
Junion G* / Spivakov M*, Girardot C, Braun M, Gustafson EH, Birney E, Furlong EE. (2012). A transcription factor collective defines cardiac cell fate and reflects lineage history. Cell, 148(3):473-86. PMID: 22304916. * joint first authors.