Dr Helen Rowe
Sir Henry Dale Research Fellow
Research in the Rowe lab focuses on the role of transposons in health and disease, which we explore through studying their control of epigenetic pathways.
Around half of our genetic content is composed of retrotransposons that are thought to be ancient viruses that have stably integrated into our genomes. These ancient viruses, as mobile genetic elements, have been drivers of evolution, creating new genes and plasticity of genomes, and many of them are species-specific.
Endogenous retroviruses are one type of retrotransposon family that resemble present day retroviruses like HIV, and as such, they are thought to have arisen from germ-line integrations of retroviruses. While these viruses that were once mobile are now mostly inactive through mutation, they have co-evolved with our genes to adopt normal functions in gene regulation. For example, exciting data including ours has shown that endogenous retroviruses retain regulatory sequences that can act as enhancers, repressors or alternative promoters for cellular genes in a temporal or tissue-specific way.
Very little is known about which transcription factors and complexes are recruited to retrotransposons though, except that several key transcription factors target repetitive sequences, like CTCF, OCT3/4 and LBP9, which has led to differences in the gene circuits controlled by these factors between species. We have set out to identify factors that target these ancient viruses in order to unravel how these pathways impact on normal gene regulation, genetic diseases and cancers.
- Tie CH, Fernandes L, Conde L, Robbez-Masson L, Sumner RP, Peacock T, Rodriguez-Plata MT, Mickute G, Gifford R, Towers GJ, Herrero J, Rowe HM. KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control. EMBO Rep. 2018;pii:e45000
- Robbez-Masson L, Tie CH, Conde L, Tunbak H, Husovsky C, Tchasovnikarova IA, Timms RT, Herrero J, Lehner PJ, Rowe HM. The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes. Genome Res. 2018;28(6):836-845
- Smith-Moore S, Neil SJD, Fraefel C, Linden RM, Bollen M, Rowe HM, Henckaerts E. Adeno-associated virus Rep proteins antagonize phosphatase PP1 to counteract KAP1 repression of the latent viral genome. Proc Natl Acad Sci U S A. 2018. pii: 201721883
- Robbez-Masson L, Tie CHC, Rowe HM. Cancer cells, on your histone marks, get SETDB1, silence retrotransposons, and go! J Cell Biol. 2017;216(11):3429-3431
- Tie CH, Rowe HM. Epigenetic control of retrotransposons in adult tissues: implications for immune regulation. Curr Opin Virol. 2017;25:28-33
- Ecco G, Cassano M, Kauzlaric A, Duc J, Coluccio A, Offner S, Imbeault M, Rowe HM, Turelli P, Trono D. Transposable Elements and Their KRAB-ZFP Controllers Regulate Gene Expression in Adult Tissues. Dev Cell. 2016;36(6):611-23
- Robbez-Masson L, Rowe HM. Retrotransposons shape species-specific embryonic stem cell gene expression. Retrovirology. 2015;12:45
- Friedli M, Turelli P, Kapopoulou A, Rauwel B, Castro-Díaz N, Rowe HM, Ecco G, Unzu C, Planet E, Lombardo A, Mangeat B, Wildhaber BE, Naldini L, Trono D. Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency. Genome Res. 2014;24(8):1251-9
- Rowe HM, Kapopoulou A, Corsinotti A, Fasching L, Macfarlan TS, Tarabay Y, Viville S, Jakobsson J, Pfaff SL, Trono D. TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells. Genome Res. 2013;23(3):452-61
- Rowe HM, Friedli M, Offner S, Verp S, Mesnard D, Marquis J, Aktas T, Trono D. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET. Development. 2013;140(3):519-29
- Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T, Maillard PV, Layard-Liesching H, Verp S, Marquis J, Spitz F, Constam DB, Trono D. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010;463(7278):237-40.