Vasily Studitsky Associate Professor UMDNJ - RWJMS Dept. of Pharmacology 675 Hoes Lane West Piscataway. NJ 08854 (732) 235-5240 FAX - 4073 studitvm@umdnj.edu

Transcription regulation; chromatin remodeling; mechanisms of enhancer and insulator action

Transcription is the first step in gene expression; the majority of eukaryotic genes are regulated at the levels of transcription initiation and/or elongation. Our research concentrate on analysis of the mechanisms and regulation of initiation and elongation using highly purified in vitro systems combined with approaches in vivo. Since defects in gene regulation are the leading causes of many human cancers. our research has direct implications for medicine.

All eukaryotic DNA is tightly condensed within small nuclei in nucleoprotein complexes called chromatin. Recently it has become clear that chromatin is a dynamic structure exploited by the cell for regulation of gene activity using a novel "histone code". We study mechanistic aspects of chromatin remodeling that occur during gene regulation and transcript elongation.

Finally. we are interested in analyzing the mechanisms of gene regulation over a large distance. Such regulation is a hallmark of regulatory pathways specific for higher eukaryotes. Two key regulatory elements are involved in regulation over a distance: enhancers and insulators. Enhancers mediate regulated gene activation over a distance; insulators are critically involved in organization of functional units of gene regulation (chromatin domains). The mechanisms of enhancer and insulator action over a distance are currently unknown.

Selected Publications

Polikanov YS, Bondarenko VA, Tchernaenko V, Jiang YI, Lutter LC, Vologodskii A, Studitsky VM. (2007) Probability of the site juxtaposition determines the rate of protein-mediated DNA looping. Biophys J. 93(8):2726-31.

Kulaeva OI, Gaykalova DA, Studitsky VM. (2007) Transcription through chromatin by RNA polymerase II: histone displacement and exchange. Mutat Res. 618(1-2):116-29.

Polikanov YS, Rubtsov MA, Studitsky VM. (2007) Biochemical analysis of enhancer-promoter communication in chromatin. Methods. 41(3):250-8. Review.

Rubtsov MA, Polikanov YS, Bondarenko VA, Wang YH, Studitsky VM. (2006) Chromatin structure can strongly facilitate enhancer action over a distance. Proc Natl Acad Sci U S A. 103(47):17690-5.

Bondarenko VA, Steele LM, Ujvari A, Gaykalova DA, Kulaeva OI, Polikanov YS, Luse DS, Studitsky VM. (2006) Nucleosomes can form a polar barrier to transcript elongation by RNA polymerase II. Mol Cell. 24(3):469-79.

Angelov D. Bondarenko VA. Almagro S. Menoni H. Mongelard F. Hans F. Mietton F. Studitsky VM. Hamiche A. Dimitrov S. Bouvet P. (2006) Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. EMBO J. 25(8):1669-79.

Kireeva ML. Hancock B. Cremona GH. Walter W. Studitsky VM. Kashlev M. (2005) Nature of the nucleosomal barrier to RNA polymerase II. Mol Cell. 18(1):97-108.

Studitsky VM. Walter W. Kireeva M. Kashlev M. Felsenfeld G. (2004) Chromatin remodeling by RNA polymerases. Trends Biochem Sci. 29(3):127-35.

Bondarenko V. Liu YV. Ninfa AJ. Studitsky VM. (2003) Assay of prokaryotic enhancer activity over a distance in vitro. Methods Enzymol. 370:324-37.

Walter. W. and Studitsky. V. M. (2004). Construction. analysis. and transcription of model nucleosomal templates. Methods. 33(1):18-24.

Liu. Y.. Clark. D.. Tchernajenko. V.. Dahmus. M. E.. and Studitsky. V. M. (2003). Role of CTD phosphorylation in transcription through the nucleosome by polymerase II. Biopolymers 68:528-38.

Walter. W.. Kireeva. M.. Studitsky. V. M.* and Kashlev. M.* (2003). Bacterial polymerase and yeast pol II use similar mechanisms for transcription through nucleosomes. J. Biol. Chem. 278:36148-56. * - corresponding authors.

Belotserkovskaya. R.. Sangtaek. O.. Bondarenko. V.A.. Orphanides. G.. Studitsky. V.M.. Reinberg. D. (2003). FACT Facilitates Transcription-Dependent Nucleosome Alteration. Science 301:1090-3.

Bondarenko. V.. Jiang. Y.. Studitsky. V.M. (2003). Rationally designed. inducible insulator can block enhancer action in vitro EMBO J. 22:4728-37.

Bondarenko. V.A.. Liu. Y.V.. Jiang. Y.I.. Studitsky. V.M. (2003). Mechanisms of enhancer action over a large distance. Biochem. Cell. Biol. 81:241-51.

Bondarenko. V.. Liu. Y.. Ninfa. A. J.. and Studitsky. V. M. (2002). Action of prokaryotic enhancer over a distance does not require continued presence of promoter-bound sigma 54 subunit. Nucleic Acids Res. 30:36-642.

Kireeva. M.. Walter. W.. Tchernajenko. V.. Bondarenko. V.. Kashlev. M.. and Studitsky. V. M. (2002). Nucleosome Remodeling Induced by RNA polymerase II: Loss of the H2A/H2B Dimer During Transcription. Mol. Cell 9:541-552.

Atkinson. M. R.. Blauwkamp. T.A.. Bondarenko. V.. Studitsky. V.. and Ninfa. A. J. (2002). Activation of the glna. glnk. and nac promoters as Escherichia coli undergoes the transition from nitrogen excess growth to nitrogen starvation. J. Bacteriol. 184: 5358-5363.

Liu. Y.. Bondarenko. V.. Ninfa. A.. and Studitsky. V. M. (2001). DNA supercoiling allows enhancer action over a large distance. Proc. Natl. Acad. Sci. U S A 98:14883-8.

Studitsky. V. M.*. Brodolin. K. L.. Liu. Y.. and Mirzabekov. A. D. (2001). Topography of lacUV5 initiation complexes. Nucleic Acids Res. 29:854-861. * - corresponding author.

Walter. W.. and Studitsky. V. M. (2001). Facilitated transcription through the nucleosome at high ionic strength occurs via a histone octamer transfer mechanism. J. Biol. Chem. 276:29104-10.

Studitsky. V. M. (2001). Transcription through chromatin. Mol. Biol. 35:235-47.