Vasily M. Studitsky, PhD
Co-Leader, Cancer Epigenetics
- PhD, Biochemistry, Institute of Molecular Biology, 1988
- MS, Biochemistry, Moscow State University, 1984
Honors & Awards
- Annual Wayne State University College Teaching Award 2002
- Annual First Prize for Research, Institute of Molecular Biology, Moscow, Russia 1988
Epigenetic mechanisms of gene expression and regulation
- Mechanisms of histone survival and exchange during Pol II transcription: role of histone chaperones and transcription factors during transcription through chromatin.
- Mechanisms of distant communication during gene regulation.
- Mechanisms of DNA repair in chromatin.
- Development of FACT- and PARP1-targeted anti-cancer drugs.
Development and functioning of higher organisms critically depends on properly regulated gene expression. Regulation of gene expression occurs primarily at the initial step (transcription) and involves DNA sequences, protein factors and dynamic changes in structure of DNA-protein complexes (chromatin). The major research goal in my laboratory is to understand the molecular mechanisms and regulation of the vital process of eukaryotic transcription in chromatin, and the role of the factors involved in cancer development and human aging (e.g. hFACT and hPARP1) in this process. This goal will be achieved using a combination of molecular genetics, genomics, biochemical, single-particle, structural and computational modeling approaches. Currently our efforts are focused in two primary directions: 1. The mechanisms of gene regulation over a distance (by enhancers & insulators), and 2. The mechanisms and regulation of transcript elongation through chromatin by RNA polymerase II.
Distant regulation of gene transcription initiation is mediated by direct interaction between proteins bound at communicating DNA elements and involves looping of intervening DNA/chromatin regions (1). Our research focuses on the following critical questions: What features of DNA/chromatin template allow efficient communication over a distance? What are distinct features of the regulatory elements that are capable of action over a distance? We have adopted relatively simple, highly purified and efficient experimental systems for quantitative analysis of enhancer action over a distance in vitro (2). This simple experimental system allowed us to identify elements of DNA and chromatin structure, as well as protein factors that mediate distant gene regulation (unpublished).
Since 1998 our studies have been focused on analysis of histone survival during transcription by Pol II (funded by NIH RO1). We have established a “minimal” experimental system that maintains single- and multiple-round transcription through various defined mono- and polynucleosomes by yeast and human RNA polymerase II (3). This system faithfully recapitulates numerous features of transcribed chromatin described in vivo and allows their molecular analysis in vitro. Using this system, we have discovered a novel Pol II-specific mechanism involving survival of core histones and their modifications without even transient histone dissociation from DNA (4). These features of the mechanism suggest that it is likely used for maintenance of chromatin structure and the “histone code” that is particularly important during genomic transcription (5,6). It is also important for chromatin-specific DNA repair (7). The most recent focus of our studies is on the mechanism of action of various elongation factors (TFIIS) and histone chaperones (hFACT & hPARP1) facilitating histone survival during Pol II transcription. Importantly, both hFACT & hPARP-1 are involved in carcinogenesis and are important targets for anti-cancer drugs.
Han-Wen Chang, MS, PhD
Ekaterina Nizovtseva, MS, PhD
Elena Kotova, MS
Daniel Sultanov, BS
Valieva, M.E., Gerasimova, N.S., Kudryashova, K.S., Kozlova, A.L., Kirpichnikov, M.P., Hu, Q., Botuyan, M.V., Mer, G., Feofanov, A.V. and Studitsky, V.M. (2017) Stabilization of Nucleosomes by Histone Tails and by FACT Revealed by spFRET Microscopy. Cancers 9, in press. PubMed
Studitsky, V.M., Nizovtseva, E.V., Shaytan, A.K. and Luse, D.S. (2016) Nucleosomal Barrier to Transcription: Structural Determinants and Changes in Chromatin Structure. Biochem Mol Biol J 2, in press. PubMed
Nizovtseva, E.V., Clauvelin, N., Polikanov, Y.S., Kulaeva, O.I., Wengrzynek, S., Olson, W.K. and Studitsky, V.M. (2016) Nucleosome-free DNA regions differentially affect distant communication in chromatin. Nucl. Acids Res., in press. PubMed
Valieva, M.E., Armeev, G.A., Kudryashova, K.S., Gerasimova, N.S., Shaytan, A.K., Kulaeva, O.I., McCullough, L.L., Formosa, T., Georgiev, P.G., Kirpichnikov, M.P., Studitsky, V.M. and Feofanov, A.V. (2016) Large-scale ATP-independent nucleosome unfolding by a histone chaperone. Nat Struct Mol Biol 23, 1111-16. PubMed
Gerasimova, N.S., Pestov, N.A., Kulaeva, O.I., Clark, D.J. and Studitsky, V.M. (2016) Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription. Transcription 7, 91-5. PubMed
Chang, H.W., Pandey, M., Kulaeva, O.I., Patel, S.S. and Studitsky, V.M. (2016) Overcoming a nucleosomal barrier to replication. Sci Adv 2, e1601865.
Pestov, N.A., Gerasimova, N.S., Kulaeva, O.I. and Studitsky, V.M. (2015) Structure of Transcribed Chromatin is a Sensor of DNA Damage. Sci. Adv. 1, e1500021.
Gaykalova, D.A., Kulaeva, O.I., Volokh, O., Shaytan, A.K., Hsieh, F.K., Kirpichnikov, M.P., Sokolova, O.S. and Studitsky, V.M. (2015) Structural Analysis of Nucleosomal Barrier to Transcription. Proc. Natl. Acad. Sci. USA, in press. PubMed
Clauvelin, N., Lo, P., Kulaeva, O.I., Nizovtseva, E.V., Diaz-Montes, J., Zola, J., Parashar, M., Studitsky, V.M. and Olson, W.K. (2015) Nucleosome positioning and composition modulate in silico chromatin flexibility. J Phys Condens Matter 27, 064112. PubMed
Chang, H.W., Kulaeva, O.I., Shaytan, A.K., Kibanov, M., Kuznedelov, K., Severinov, K.V., Kirpichnikov, M.P., Clark, D.J. and Studitsky, V.M. (2014) Analysis of the mechanism of nucleosome survival during transcription. Nucleic Acids Res. 42, 1619-27. PubMed
Hsieh, F.K., Kulaeva, O.I., Patel, S.S., Dyer, P.N., Luger, K., Reinberg, D. and Studitsky, V.M. (2013) Histone chaperone FACT action during transcription through chromatin by RNA polymerase II. Proc. Natl. Acad. Sci. USA 110, 7654-9. PubMed