Senior Lecturer, Department of Human Molecular Genetics and Biochemstry, Sackler Faculty of Medicine
Senior Lecturer, Department of Human Molecular Genetics and Biochemstry, Sackler Faculty of Medicine
Genomic-scale Bioinfomatics Exploration of Gene Regulation
Our research focuses on understanding mechanisms of gene regulation, which is an intricate multi-layer process. We apply bioinofrmatics methods to elucidate, on a genomic scale, how gene expression is regulated at the layers of gene transcription, transcript stability and protein translation. We aim at discovering how interruptions in these regulatory mechanisms contribute to the development of human pathological conditions, and how natural genomic variation affects our predisposition to common human diseases. Our analyses are based on novel deep-sequencing techniques that greatly boost our ability to systematically study gene regulation and decipher regulatory layers that were until recently largely unexplored.
Korkmaz G, Lopes R, Ugalde AP, Nevedomskaya E, Han R, Myacheva K, Zwart W, Elkon R*, Agami R*. Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nat Biotechnol. 2016, 34:192-8. (* Co-corresponding author)
Friedman-Mazursky O, Elkon R, Efrat S. Redifferentiation of expanded human islet β cells by inhibition of ARX. Sci Rep. 2016; 6:20698.
Creemers EE, Bawazeer A, Ugalde AP, van Deutekom HW, van der Made I, de Groot NE, Adriaens ME, Cook SA, Bezzina CR, Hubner N, van der Velden J, Elkon R, Agami R, Pinto YM. Genome-wide polyadenylation maps reveal dynamic mrna 3’-end formation in the failing human heart. Circ Res. 2016, 118:433-8.
Elkon R*, Loayza-Puch F*, Korkmaz G, Lopes R, Breugel PCv, Bleijerveld OB, Altelaar AFM, Wolf E, Lorenzin F, Eilers M, Agami R: Myc coordinates transcription and translation to enhance transformation and suppress invasiveness. EMBO Rep. 2015, pii: e201540717. (*Equal contribution).
Elkon R*, Milon B*, Morrison L, Shah M, Vijayakumar S, Racherla M, Leitch CC, Silipino L, Hadi S, Weiss-Gayet M, Barras E, Schmid CD, Ait-Lounis A, Barnes A, Song Y, Eisenman DJ, Eliyahu E, Frolenkov GI, Strome SE, Durand B, Zaghloul NA, Jones SM, Reith W, Hertzano R. RFX transcription factors are essential for hearing in mice. Nat Commun 2015, 6:8549. (*Equal contribution).
Rashi-Elkeles S*, Warnatz HJ*, Elkon R*, Kupershtein A, Chobod Y, Paz A, Amstislavskiy V, Sultan M, Safer H, Nietfeld W, Lehrach H, Shamir R, Yaspo ML, Shiloh Y. Parallel profiling of the transcriptome, cistrome, and epigenome in the cellular response to ionizing radiation. Sci Signal. 2014, 7:rs3. (*Equal contribution).
Loayza-Puch F, Drost J, Rooijers K, Lopes R, Elkon R*, Agami R*. p53 induces transcriptional and translational programs to suppress cell proliferation and growth. Genome Biol. 2013, 14:R32. (*co-corresponding authors).
Melo CA, Drost J, Wijchers PJ, van de Werken H, de Wit E, Oude Vrielink JA, Elkon R, Melo SA, Leveille N, Kalluri R, de Laat W, Agami R. eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell. 2013, 49:524-35.
Elkon R*, Drost J*, van Haaften G, Jenal M, Schrier M, Vrielink JA, Agami R. E2F mediates enhanced alternative polyadenylation in proliferation. Genome Biol. 2012, 13:R59. (*Equal contribution).
Morris AR, Bos A, Diosdado B, Rooijers K, Elkon R, Bolijn AS, Carvalho B, Meijer GA, Agami R. Alternative cleavage and polyadenylation during colorectal cancer development. Clin Cancer Res. 2012, 18:5256-66.
Jenal M*, Elkon R*, Loayza-Puch F, van Haaften G, Kahn U, Menzies FM, Oude Vrielink JA, Bos AJ, Drost J, Rooijers K, Rubinsztein DC, Agami R. The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell. 2012, 149:538-53. (*Equal contribution).
Léveillé N, Elkon R, Davalos V, Manoharan V, Hollingworth D, Oude Vrielink J, le Sage C, Melo CA, Horlings HM, Wesseling J, Ule J, Esteller M, Ramos A, Agami R. Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity. Nat Commun. 2011, 2:513.
Hertzano R, Elkon R, Kurima K, Morrisson A, Chan SL, Sallin M, Biedlingmaier A, Darling DS, Griffith AJ, Eisenman DJ, Strome SE. Cell type-specific transcriptome analysis reveals a major role for Zeb1 and miR-200b in mouse inner ear morphogenesis. PLoS Genet. 2011, 7:e1002309.
Salton M, Elkon R, Borodina T, Davydov A, Yaspo ML, Halperin E, Shiloh Y. Matrin 3 binds and stabilizes mRNA. PLoS One. 2011, 6:e23882.
Rashi-Elkeles S, Elkon R, Shavit S, Lerenthal Y, Linhart C, Kupershtein A, Amariglio N, Rechavi G, Shamir R, Shiloh Y. Transcriptional modulation induced by ionizing radiation: p53 remains a central player. Mol Oncol. 2011, 5:336-48.
Elkan-Miller T, Ulitsky I, Hertzano R, Rudnicki A, Dror AA, Lenz DR, Elkon R, Irmler M, Beckers J, Shamir R, Avraham KB. Integration of transcriptomics, proteomics, and microRNA analyses reveals novel microRNA regulation of targets in the mammalian inner ear. PLoS One. 2011;6:e18195.
Paz A, Brownstein Z, Ber Y, Bialik S, David E, Sagir D, Ulitsky I, Elkon R, Kimchi A, Avraham KB, Shiloh Y, Shamir R. SPIKE: a database of highly curated human signaling pathways. Nucleic Acids Res. 2011, 39(Database issue):D793-9.