Dr Tatiana (Tanya) Soboleva
Areas of expertise
- Epigenetics (Incl. Genome Methylation And Epigenomics) 060404
- Developmental Genetics (Incl. Sex Determination) 060403
- Neurogenetics 060410
- Cell Development, Proliferation And Death 060103
- Biochemistry And Cell Biology 0601
Research interests
Our group is interested in research that connects epigenetics, cell differentiation and cancer. Epigenetic mechanisms control our genome and ensure that every cell expresses a certain set of genes that defines its cell type specificity. Epigenetic control of the genome has to be dynamic and rigid at the same time, to ensure that the cell maintains its function but can adapt to developmental or environmental changes. The flaws in these finely tuned epigenetic mechanisms can be very detrimental and lead to disease states including cancer.
Our research is focused on study of epigenetic control of normal developmental processes, using spermatogenesis (the development and differentiation of male germ cells) as an excellent differentiation model system. On the other hand, we study how epigenetic deregulation is involved in cancer development, examining germ-cell specific epigenetic regulators, that are aberrantly overexpressed in cancer.
Majority of our research is focused around an epigenetic regulator that was discovered in our laboratory, the histone variant H2A.B, that is testis and brain-specific. This histone variant is targeted to the transcription start sites (TSSs) to co-ordinately activates transcription by a chromatin ‘opening’ mechanism. More recently, we showed that H2A.B can directly bind RNA and is involved in pre-mRNA splicing. This was a major paradigm shift because it showed for the first time that a histone could not only interact directly with DNA but also with RNA. To study H2A.B function, we generated a H2A.B KO mouse model and showed that downregulation of H2A.B affects male fertility and brain function. The unique ability of H2A.B histone to interact with DNA and RNA as well as the RNA processing machinery, opens up a whole new field of research that will provide new insights into the epigenetic regulation.
The Cancer and Germ Cell Epigenetics Group closely collaborates with The Chromatin and Translational Regulation group, led by Prof Tremethick. We have a number of current and potential projects that aim to uncover previously unreported mechanisms of epigenetic control coordinated by H2A.B. See JCSMR student projects for details.
Biography
Dr Tatiana (Tanya) Soboleva received her undergraduate training in biochemistry at the Moscow State University. In 1998 she was awarded an International Postgraduate Research Scholarship by the Australian Government. She undertook her PhD study at the JCSMR, ANU, with Dr. Rohan Baker and was awarded a PhD in Molecular Medicine for her work investigating nucleocytoplasmic transport of the de-ubiquitilating enzyme, Usp4. In 2003 she undertook post-doctoral studies with Prof. Ian Young (JCSMR, ANU), investigating how the cytokines activate their receptor systems. In 2006 she joined Prof. David Tremethick’s laboratory (JCSMR, ANU). Together with Prof. Tremethick, she discovered a novel histone variant, which is involved in the activation of genes expressed during specific stages of spermatogenesis. Since 2012, Dr Soboleva established a subgroup in Prof. Tremethick's laboratory and an independent group in 2019. Our collaborative work is based on undertsadning of functions of spermatogenesis-specific epigenetic factors as well as their role when they become upregulated in various cancers.
Available student projects
There is a number of long and short-term research projects available for PhD, MPhil, Honours and undergraduate students. Please contact Dr. Soboleva for details (tanya.soboleva@anu.edu.au).
Current student projects
- Evaluate the role of testis-specific histone variant, H2A.Bbd, in Hodgkin lymphoma carcinogenesis.
- Develop new avenues for early detection of Hodgkin Lymphoma patients who are likely to relapse under current treatment regiments.
- Develop new avenues for Hodgkin lymphoma treatment.
- A novel mechanism of long-term memory formation that involves testis-specific histone variant expression in the brain.
- Elucidate the role of a testis-specific histone variant expression in the Purkinje neurons of mouse cerebellum.
- Characterization of H2A.Lap1 KO mice spermatogenesis following heat stress or gamma irradiation.
Publications
- Jiang, X, Wen, J, Paver, E et al. 2021, 'H2A.B is a cancer/testis factor involved in the activation of ribosome biogenesis in Hodgkin lymphoma', EMBO Reports, vol. 22, no. 8.
- Jiang, X, Soboleva, T & Tremethick, D 2020, 'Short Histone H2A Variants: Small in Stature but not in Function', Cells, vol. 9, no. 4, pp. 1-12.
- Anuar, N, Kurscheid, S, Field, M et al 2019, 'Gene editing of the multi-copy H2A.B gene and its importance for fertility 06 Biological Sciences 0604 Genetics Jin-Soo Kim', Genome Biology, vol. 20, no. 1, pp. -.
- Soboleva, T & Tremethick, D 2018, 'RChIP-Seq: Chromatin-Associated RNA Sequencing in Developmentally Staged Mouse Testes', in Guillermo A. Orsi and Geneviève Almouzni (ed.), Histone Variants: Methods and Protocols, Humana Press, New York, pp. 169-184.
- Soboleva, T, Parker, B, Nekrasov, M et al 2017, 'A new link between transcriptional initiation and pre-mRNA splicing: The RNA binding histone variant H2A.B', PLoS Genetics, vol. 13, no. 2, pp. e1006633-e1006633.
- Moretti, C, Serrentino, M, Ialy-Radio, C et al 2017, 'SLY regulates genes involved in chromatin remodeling and interacts with TBL1XR1 during sperm differentiation', Cell Death and Differentiation, vol. 24, no. 6, pp. 1029-1044.
- Soboleva, T, Nekrasov, M, Ryan, D et al 2014, 'Histone variants at the transcription start-site', Trends in Genetics, vol. 30, no. 5, pp. 199-209.
- Soboleva TA, Nekrasov M, Ryan DP, Tremethick DJ. Histone variants at the transcription start-site. Trends Genet. 2014 May;30(5):199-209
- Nekrasov, M, Soboleva, T, Jack, C et al 2013, 'Histone variant selectivity at the transcription start site H2A.Z or H2A.Lap1', Nucleus, vol. 4, no. 6, pp. 431-437.
- Nekrasov, M, Amrichova, J, Parker, B et al., 'Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics', Nature Structural and Molecular Biology. 2012, vol. 19, no. 11, pp. 1076-1083.
- Soboleva TA, Nekrasov M, Pahwa A, Williams R, Huttley GA, Tremethick DJ. 'A unique H2A histone variant occupies the transcriptional start site of active genes', Nature Structural and Molecular Biology. 2012 Jan; 19(1): 25-30.
- Murphy, J, Soboleva, T, Mirza, S et al 2008, 'Clarification of the role of N-glycans on the common beta-subunit of the human IL-3, IL-5 and GM-CSF receptors and the murine IL-3 beta-receptor in ligand-binding and receptor activation', Cytokine, vol. 42, no. 2, pp. 234-42.
- Soboleva, T, Jans, D, Johnson-Saliba, M et al. 2005, 'Nuclear-Cytoplasmic Shuttling of the Oncogenic Mouse UNP/USP4 Deubiquitylating Enzyme', Journal of Biological Chemistry, vol. 280, no. 1, pp. 745-752.
- Baker, R, Catanzariti, A, Karunasekara, Y et al 2005, 'Using Deubiquitylating Enzymes as Research Tools', in Raymond J. Deshaies (ed.), Ubiquitin and Protein Degradation, Elsevier, California, pp. 540-554.
- Catanzariti, A, Soboleva, T, Jans, D et al. 2004, 'An efficient system for high-level expression and easy purification of authentic recombinant proteins', Protein Science, vol. 13, pp. 1331-1339.
- Soboleva, T & Baker, R 2004, 'Deubiquitinating Enzymes: Their Functions and Substrate Specificity', Current Protein and Peptide Science, vol. 5, pp. 191-200.
