Publications

1. 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. 2018. KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control. EMBO Rep 19.

doi:10.15252/embr.201745000.

We asked if KAP1 is necessary to suppress endogenous retroviruses (ERVs) in human adult cells and reasoned that once reactivated, ERVs may stimulate an innate or adaptive immune response. We reveal here that KAP1 inactivation leads to ERV upregulation and induction of an RNA-sensing innate immune response.

 

2. Robbez-Masson L, Tie CHC, Conde L, Tunbak H, Husovsky C, Tchasovnikarova IA, Timms RT, Herrero J, Lehner PJ, Rowe HM. 2018. The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes. Genome Res doi:10.1101/gr.228171.117.

We identify the HUSH complex as necessary to silence recently-integrated genome invaders such as young L1 elements in early development. We additionally reveal that the HUSH complex and KAP1 co-regulate some recently evolved and tissue-specific genes.

 

3. Smith-Moore S, Neil SJD, Fraefel C, Linden RM, Bollen M, Rowe HM, Henckaerts E. 2018. Adeno-associated virus Rep proteins antagonize phosphatase PP1 to counteract KAP1 repression of the latent viral genome. Proc Natl Acad Sci U S A doi:10.1073/pnas.1721883115.

We find that KAP1 blocks AAV replication but is usually counteracted by viral Rep proteins.

 

4. Robbez-Masson L, Tie CHC, Rowe HM. 2017. Cancer cells, on your histone marks, get SETDB1, silence retrotransposons, and go! J Cell Biol 216:3429-3431.

Invited spotlight on an article showing that SETDB1 expression is elevated in cancers to promote their immune evasion through silencing retrotransposons.

 

5. Tie CH, Rowe HM. 2017. Epigenetic control of retrotransposons in adult tissues: implications for immune regulation. Curr Opin Virol 25:28-33.

Invited review on epigenetic regulation in adult tissues.

 

6. Ecco G, Cassano M, Kauzlaric A, Duc J, Coluccio A, Offner S, Imbeault M, Rowe HM, Turelli P, Trono D. 2016. Transposable Elements and Their KRAB-ZFP Controllers Regulate Gene Expression in Adult Tissues. Dev Cell 36:611-623.

We perform a screen for novel transcription factors (KRAB-ZFPs) targeting endogenous retroviruses and characterize several that regulate some cellular genes through binding to retroviral sequences.

 

7. Ecco G, Rowe HM, Trono D. 2016. A Large-Scale Functional Screen to Identify Epigenetic Repressors of Retrotransposon Expression. Methods Mol Biol 1400:403-417.

We setup a method to identify novel KRAB-ZFP repressors of ERVs, which we describe here.

 

8. Robbez-Masson L, Rowe HM. 2015. Retrotransposons shape species-specific embryonic stem cell gene expression. Retrovirology 12:45.

Invited review illustrating how transposon-derived DNA sequences can act as enhancers or repressors in ESCs depending on the transcription factors they recruit.

 

9. Friedli M, Turelli P, Kapopoulou A, Rauwel B, Castro-Diaz N, Rowe HM, Ecco G, Unzu C, Planet E, Lombardo A, Mangeat B, Wildhaber BE, Naldini L, Trono D. 2014. Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency. Genome Res 24:1251-1259.

We characterize retroelement reactivation that we note occurs during reprogramming.

 

10. Corsinotti A, Kapopoulou A, Gubelmann C, Imbeault M, Santoni de Sio FR, Rowe HM, Mouscaz Y, Deplancke B, Trono D. 2014. Global and stage specific patterns of Kruppel-associated-box zinc finger protein gene expression in murine early embryonic cells. PLoS One 8:e56721.

We characterize expression patterns of KRAB-ZFPs, some of which mediate transposon control.

 

11. Rowe HM, Friedli M, Offner S, Verp S, Mesnard D, Marquis J, Aktas T, Trono D. 2013. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET. Development 140:519-529.

Initiation of retroviral silencing leads to rapid de novo DNA methylation in mouse embryonic stem cells and in vivo in mouse development.

 

12. Rowe HM, Kapopoulou A, Corsinotti A, Fasching L, Macfarlan TS, Tarabay Y, Viville S, Jakobsson J, Pfaff SL, Trono D. 2013. TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells. Genome Res 23:452-461.

KAP1 silences long terminal repeats (LTRs) and its inactivation leads to ectopic expression of nearby genes partly by revealing cryptic LTR enhancers. This raises the possibility that the same LTRs may be naturally dynamically controlled to regulate gene expression programmes.

 

13. Macfarlan TS, Gifford WD, Driscoll S, Lettieri K, Rowe HM, Bonanomi D, Firth A, Singer O, Trono D, Pfaff SL. 2012. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487:57-63.

The retrovirus MERVL drives expression of 2-cell stage-expressed genes and stem cell potency can be controlled by manipulating epigenetic machinery that regulates MERVL.

 

14. Rowe HM, Trono D. 2011. Dynamic control of endogenous retroviruses during development. Virology 411:273-287.

Invited review dissecting retroviral epigenetic regulation in development.

 

15. 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. 2010. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463:237-240.

Much of mammalian genomes are composed of transposable elements, which we uncover to be controlled by KAP1/TRIM28 in early development.

 

16. Arce F, Rowe HM, Chain B, Lopes L, Collins MK. 2009. Lentiviral vectors transduce proliferating dendritic cell precursors leading to persistent antigen presentation and immunization. Mol Ther 17:1643-1650.

We discover that cancer vaccines based on lentivectors cause persistent antigen presentation in vivo by naturally targeting dendritic cell precursors.

 

17. Rowe HM, Lopes L, Brown N, Efklidou S, Smallie T, Karrar S, Kaye PM, Collins MK. 2009. Expression of vFLIP in a lentiviral vaccine vector activates NF-{kappa}B, matures dendritic cells, and increases CD8+ T-cell responses. J Virol 83:1555-1562.

We employ a viral protein, vFLIP to act as an intrinsic adjuvant in a cancer vaccine through its constitutive activation of NFkB.

 

18. Rowe HM, Lopes L, Ikeda Y, Bailey R, Barde I, Zenke M, Chain BM, Collins MK. 2006. Immunization with a lentiviral vector stimulates both CD4 and CD8 T cell responses to an ovalbumin transgene. Mol Ther 13:310-319.

We design cancer vaccines to encode antigens that will be presented on both MHC class I and II to enhance anti-tumour immunity.