Structure of eukaryotic chromatin
The nucleosome as structural unit of chromatin is sufficiently stable to maintain structures of higher order. At the same time, it must ensure the availability the information encoded in the DNA. Much data allows us to consider the nucleosome as a dynamic structure that can reversibly change its conformation and composition. We have studied mononucleosomes reconstituted from a DNA core histone octamer by atomic force microscopy (AFM) and found their remarkable structural diversity caused by disassembly of octasome and formation of subnucleosomal structures. These structures were due to the quantized DNA unwrapping and partial histone octamer dissociation. The equilibrium of these subpopulations was significantly affected by ionic environment (manuscript in preparation). The observed nucleosome structural diversity serves as a paradigm of their functional plasticity dictated by physiological environment.

Elena KUZMINA
Student
krista-sojka@yandex.ru

Ekaterina SYTNIK
Student
eksytnik@yandex.ru

Anastasia PASHUTOVA
Student
pashutova@ya.ru

Alexandra Kondrashkina, currently working for a company, alex_sandra2502@mail.ru;
Dr. Elena Tolkunova, currently head of Cancer Stem Cell group, Institute of Cytology RAS, entolk62@mail.ru;
Dr. Mikhail Liskovykh, currently post-doc, National Cancer Institute, NIH, Bethesda, USA;
Dr. Alexander Davydov-Sinitsyn, currently working for a company;
Dina Safina, currently PhD student, Department for Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany;
Lyubov Chechik, currently PhD student Max-Planck Institute of Immunobiology and Epigenetics, Freiburg (Germany);
Dr. Anna Malashicheva, currently Head of Laboratory, Almazov Federal Heart, Blood and Endocrinology Centre, St-Petersburg (Russia);
Birgit Koschortz, MPI-Freiburg;
Robert Turek, MPI-Freiburg;
Volker Koelin, MPI-Freiburg

Cherepanova OA , Gomez D, Shankman LS, Swiatlowska P, Williams O, Sarmento OF, Alencar GF, Hess DL, Bevard MH, Greene ES, Murgai M, Turner SD, Geng YJ, Bekiranov S, Connelly JJ, Tomilin A, Owens GK (2016) Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. Nat Medicine, published online 16 May 2016; doi:10.1038/nm.4109

Kostina AS, Uspensky VЕ, Irtyuga OB, Ignatieva EV, Freylikhman O, Gavriliuk ND, Moiseeva OM, Zhuk S, Tomilin A, Kostareva АА, Malashicheva AB (2016) Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve. Biochim Biophys Acta. 2016 Feb 10. pii: S0925-4439(16)30032-1. doi: 10.1016/j.bbadis.2016.02.006. [Epub ahead of print]

Nazarov I, Chekliarova I, Rychkov G, Ilatovskiy AV, Crane-Robinson C, Tomilin A. (2016) AFM studies in diverse ionic environments of nucleosomes reconstituted on the 601 positioning sequence. Biochimie 121: 5-12.

Liskovykh M, Ponomartsev S, Popova E, Bader M, Kouprina N, Larionov V, Alenina N, Tomilin A. (2015) Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice. Cell Cycle 4(8):1268-73.

Kulichkova VA, Artamonova TO, Zaykova JJ, Ermolaeva JB, Khodorkovskii MA, Barlev NA, Tomilin A, Tsimokha AS (2014) Simultaneous EGFP and Tag Labeling of the b7 Subunit for Live Imaging and Affinity Purification of Functional Human Proteasomes. Mol Biotechnol. Aug 28. [Epub ahead of print].

Bajenova O, Chaika N, Tolkunova E, Davydov-Sinitsyn A, Gapon S, Thomas P, O'Brien S. (2014) Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes. Exp Cell Res. Epub 2014 Apr 12.

Kouprina N, Tomilin A, Masumoto H, Earnshaw WC, Larionov V. (2014) HAC-based gene delivery vectors for gene function studies, gene therapy and pharmacology. Expert Opin. Drug Del. 11 (4): 1-19.

Yang CS, Sinenko SA, Thomenius MJ, Robeson AC, Freel CD, Horn SR, Kornbluth S. The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis. Cell Death Differ. 2014 Apr;21(4):604-11. doi: 10.1038/cdd.2013.184. Epub 2013 Dec 20.

DeVeale B, Brokhman I, Mohseni P, Babak T, Yoon C, Lin A, Onishi K, Tomilin A, Pevny L, Zandstra PW, Nagy A, van der Kooy D (2013) Oct4 is required for e7.5 for proliferation in the primitive streak. PLoS Genet. 9(11): e1003957.

Wu G, Han D, Gong Y, Sebastiano V, Gentile L, Singhal N, Adachi K, Fischedick G, Ortmeier C, Sinn M, Radstaak M, Tomilin A, Schöler HR. (2013) Establishment of totipotency does not depend on Oct4. Nat Cell Biol. 15(9): 1089-97.

Lee N.C.O, K. A., Lee H.S, Tolkunova E.N., Liskovykh М.A., Masumoto H., Earnshaw W.C., Tomilin A., Larionov V., Kouprina N. (2013) Protecting a transgene expression from the HAC-based vector by different chromatin insulators. Cell. Mol. Life Sci. 70(19): 3723-37.

Nazarov I, Krasnoborova V, Mitenberg A, Chikhirzhina E, Davidov-Sinitsin A, Liskovykh M, and Tomilin A (2014) Transcription Regulation of Oct4 (Pou5F1) Gene by Its Distal Enhancer. Cell and Tissue Biol 8(1): 27-32.

Davydov-Sinitsyn A, O. V. Bazhenova, M. A. Liskovykh, L. L. Chechik, S. V. Ponomartsev S, Tomilin A, Tolkunova E. (2013) In vitro Derivation and Characterization of a Colorectal Cancer Stem Cell Subpopulation. Cell and Tissue Biol 7(4): 320-325.

Davydov-Sinitsyn A, Bajenova O, Liskovykh M, Ponomartsev S, Chechik L, Tomilin A, Tolkunova E. (2012) Comparative Analysis of Colorectal Carcinoma Cell Lines That Differ in Metastatic Potential. Cell and Tissue Biol 7(5): 407-412.

Liskovykh M., Chuykin I., Ranjan A., Safina D., Popova E., Tolkunova E., Mosienko V., Minina J., Zhdanova N., Mullins J.J., Bader B., Alenina N., Tomilin A. (2011) Derivation, characterization, and stable transfection of induced pluripotent stem cells from Fischer344 rats. PLoS ONE 11 (6): e27345.

Liskovykh M, Davydov-Sinitcyn A, Marilovtceva E, Tomilin A, Tolkunova E. (2011) Interaction between the CDX2 Transcription Factor and DDX5 Protein. Cell and Tissue Biol. 6(1): 20-25.

Mondal BC, Mukherjee T, Mandal L, Evans CJ, Sinenko SA, Martinez-Agosto JA, Banerjee U. (2011) Interaction between differentiating cell- and niche-derived signals in hematopoietic progenitor maintenance. Cell 147(7): 1589-600.

Sinenko SA, Shim J, Banerjee U. (2011) Oxidative stress in the haematopoietic niche regulates the cellular immune response in Drosophila. EMBO Rep. 13(1):83-9

Sinenko SA, Hung T, Moroz T, Tran QM, Sidhu S, Cheney MD, Speck NA, Banerjee U (2010) Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model. Blood 116(22): 4612-20.U.

Before 2010

Kuckenberg P., Buhl S., Woynecki T., van Fürden B., Tolkunova E., Seiffe F., Moser M., Tomilin A., Winterhager E., Schorle H. (2010) The transcription factor TCFAP2C/AP-2gamma cooperates with CDX2 to maintain trophectoderm formation. Mol. Cell. Biol. 30: 3310-3320. [ download ]

Tomilin A., Tolkunova E., Liskovykh M. (2009) A method of stem cell application for tissue-replacement therapies. 2009 Russian Federation patent application (2009143025).

Saxe J., Tomilin А., Schöler H.R., Plath K., Huang J. (2009) Post-Translational Regulation of Oct4 Transcriptional Activity. PLOS One 4: 1-9. [ download + supplement ]

Tolkunova E., Malashicheva A., Chikhirzhina E., Kostyleva E., Zeng W., Luo J., Dobrinski I., Hierholzer A., Kemler R., and Tomilin A. (2009) E-Cadherin as a Novel Surface Marker of Spermatogonial Stem Cells. Cell and Tissue Biol. 3: 103-109. [ download ]

Popov B., Petrov N., Mikhailov V., Tomilin A., Alekseenko L., Grinchuk T., and Zaichik A. (2009) Spontaneous Transformation and Immortalization of Mesenchymal Stem Cells in vitro. Cell and Tissue Biol. 3: 110-115.

Sinenko SA, Mandal L, Martinez-Agosto JA, Banerjee U. (2009) Dual role of wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila. Dev Cell 16(5): 756-63.

Tolkunova A., Malashicheva A., Parfenov V.N., Sustmann C., Grosschedl R., Tomilin A. (2007) PIAS proteins as repressors of Oct4 function. J. Mol. Biol. 374: 1200-1212. [ download + supplement ]

Lengner C.J., Camargo F.D., Hochedlinger K., Welstead G.G., Zaidi S., Gokhale S., Schöler H.R., Tomilin A., Jaenisch R. (2007) Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell Stem Cell 1: 403-415. [ download + supplement ]

Malashicheva A., Kanzler B., Tolkunova E., Trono D., Tomilin A. (2007) Lentivirus as a tool for lineage-specific gene manipulations. Genesis 45, 456-459. [ download + supplement ]

Tolkunova E., Cavaleri F., Eckardt S., Reinbold R., Christenson L.K., Schöler H.R. , Tomilin A. (2006) The Caudal-Related Protein Cdx2 Promotes Trophoblast Differentiation of Mouse ES Cells. Stem Cells 24: 139-144. [ download + supplement ]

Kehler J, Tolkunova E., Koschorz B., Pesce M., Gentile L., Boiani M, Lomeli H, Nagy A, McLaughlin K.J., Schöler H.R., Tomilin A. (2004) Oct4 is required for primordial germ cell survival. EMBO Rep. 5: 1078-83. [ download + supplement ]

Lins K., Reményi A., Tomilin A., Massa S., Wilmanns M., Matthias P. and Schöler H.R. (2003) OBF1 enhances transcriptional potential of Oct1. EMBO J. 22: 2188-2198. [ download ]

Seralini G.E., Tomilin A., Auvray P., Nativelle-Serpentini C., Sourdaine P., Moslemi S. (2003) Molecular characterization and expression of equine testicular cytochrome P450 aromatase. Biochim Biophys Acta. 1625: 229-238. [ download ]

Kobayashi M., Fujioka M., Tolkunova E., D. Deka, M. Abu-Shaar, R. S. Mann, and J.B. Jaynes. (2003) Engrailed cooperates with extradenticle and homothorax to repress target genes in Drosophila. Development 130: 741-51. [ download ]

Remenyi A, Tomilin A, Schöler HR, Wilmanns M. (2002) Differential activity by DNA-induced quarternary structures of POU transcription factors. Biochem Pharmacol. 64: 979-84. [ download ]

Perez-Martinez X, Funes S, Tolkunova E, Davidson E, King MP, Gonzalez-Halphen D. (2002) Structure of nuclear-localized cox3 genes in Chlamydomonas reinhardtii and in its colorless close relative Polytomella sp. Curr Genet. 40: 399-404. [ download ]

*Remenyi A., *Tomilin A., Pohl E., Lins K., Philippsen A., Reinbold R., Scholer H.R., and Wilmanns M. (2001) Differential transcriptional activity of dimeric Oct-1 by DNA-motif induced domain swapping. Mol. Cell 8: 569-580. [ download ]
* equal contributors

Perez-Martinez X., Antaramian A., Vazquez-Acevedo M, Funes S, Tolkunova E, d'Alayer J, Claros MG, Davidson E, King MP, Gonzalez-Halphen D. (2001) Sububunit II of cytochrome c oxidase in Chlamydomonad algae is a heterodimer encoded by two independent nuclear genes. J Biol Chem 276: 11302-9. [ download ]

^#Tomilin A., ^#Remenyi A., Lins K., Bak H., Leidel S., Vriend G., Wilmanns M., Schöler H.R. (2000) Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell 103: 853-864. [ download ]
^# equal contributors

Perez-Martinez X., Vazquez-Acevedo M., Tolkunova E., Funes S., Claros MG, Davidson E., King D., Gonzales-Halphen D. (2000) Unusual location of mitochondrial gene. Subunit III of cytochtome C oxidase is encoded in the nucleus of C. algae. J Biol Chem. 275: 30144-30152. [ download ]

Tolkunova E., Park H., Xia J., King MP., Davidson E. (2000) The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript. J Biol Chem 275: 35063-35069. [ download ]

Kropotov A., Sedova V., Ivanov V., Sazeeva N., Tomilin A., Krutilina R., Oei S.L., Griesenbeck J., Buchlow G., Tomilin N. (1999) A novel human DNA-binding protein with sequence similarity to a subfamily of redox proteins which is able to repress RNA-polymerase-III-driven transcription of the Alu-family retroposons in vitro. Eur. J. Biochem. 260: 336-346.

Tomilin A., Vorob'ev V., Drosdowsky M., Seralini G.-E. (1998) Oct3/4-associating proteins from embryonal carcinoma and spermatogenic cells of mouse. Mol. Biol. Rep. 25: 103-109.

Tolkunova E., Fujioka M., Kobayashi M., Deka D., Jaynes J. (1998) Two distinct types of repression domain in engrailed: one interacts with groucho co-repressor and is preferentially active in integrated target genes. Mol. Cell. Biol. 18 (5): 2804-2814. download.

Belokopytova I.A., Kostyleva E.I., Tomilin A., Vorob'ev V.I. (1993) Human male infertility may be due to a decrease of the protamine P2 content in sperm chromatin. Mol. Reprod. Dev. 34: 53-57.