Epigenetics of the Cell Nucleus

Epigenetics of the Cell Nucleus

Prof., RNDr. Pavel Hozák, DrSc. — Project head

About us

The project will focus on chromosome dynamics during gametogenesis in two eukaryotic models (C. elegans, M. musculus). The main direction of research will address the proteins involved in early meiotic stages during pairing and synapsis of homologous chromosomes.

 Identification of new players affecting meiosis during gametogenesis is clearly very important, timely endeavor as the chromosomal dynamics and possible complications during meiotic divisions still remain incompletely understood. Yet, inaccuracies during meiotic stages are connected to chromosomal aberrations leading to severe genetic disorders as well as to male infertility.

In our preliminary experiments, we showed that vinculin/DEB-1 clearly participates in meiotic prophase progression. A depletion of DEB-1 impacts chromosomal pairing stabilization, attachment of chromosomes to cytoskeletal forces, and formation of synaptonemal complex during prophase I, resulting in meiosis delay and increased presence of chromosome univalents. Our study thus revealed an unsuspected role of DEB-1 in the progression of meiotic prophase, including chromosome dynamics and pairing that have been shown to be an essential meiotic components.

So far, nuclear functions of vinculin/DEB-1 have not been described at all, and in this project we suggest accomplishing a systematic study using a panel of structural, molecular and genetic methods in order to reveal details about its biological functions in the cell nucleus, and in meiosis in particular. We plan to achieve two main aims: Aim 1/ Mapping of vinculin at meiosis-specific structures in cell nuclei; Aim 2/Decipherment the meiosis-specific roles of vinculin and associated proteins.

Meiosis is a key process for sexual reproduction contributing to the genetic variability of organisms. Deciphering the roles of novel components of the synaptonemal complex would therefore significantly contribute to our understanding of the molecular mechanisms and dynamics of meiotic events, and may possibly also help to explain some of the fertility deficiencies, which are a prominent medial problem affecting 10 % of humans.

Publications

2017

Dong, L. F., Kovarova, J., Bajzikova, M., Bezawork-Geleta, A., Svec, D., Endaya, B., Sachaphibulkij, K., Coelho, A. R., Sebkova, N., Ruzickova, A., Tan, A. S., Kluckova, K., Judasova, K., Zamecnikova, K., Rychtarcikova, Z., Gopalan, V., Sobol, M., Yan, B., Pattnaik, B., Bhatraju, N., Truksa, J., Stopka, P., Hozak, P., Lam, A., Sedlacek, R., Oliveira, P. J., Kubista, M., Agrawal, A., Dvorakova-Hortova, K., Rohlena, J., Berridge, M. V., Neuzil, J. Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. eLife, 6:e22187, 2017. doi: 10.7554/eLife.22187. ISSN 2050-084X.

Dráberová E, Sulimenko V, Vinopal S, Sulimenko T, Sládková V, D'Agostino L, Sobol M, Hozák P, Křen L, Katsetos CD, Dráber P: Differential expression of human γ-tubulin isotypes during neuronal development and oxidative stress points to a γ-tubulin-2 prosurvival function FASEB JOURNAL 2017 31(5): 1828-1846.

Fabrik I, Link M, Putzova D, Plzakova L, Lubovska Z, Philimonenko V, Pavkova I, Rehulka P, Krocova Z, Hozak P, Santic M, Stulik J: The early dendritic cell signaling induced by virulent Francisellatularensis strain occurs in phases and involves the activation of ERKs and p38 in the later stage. Mol Cell Proteomics 2017.

Fišerová J, Efenberková M, Sieger T, Maninová M, Uhlířová J, Hozák P: Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data. J Cell Sci 2017 130(12): 2066-2077.

Morales J, Sobol M, Rodriguez-Zapata LC, Hozak P, Castano E: Aromatic amino acids and their relevance in the specificity of the PH domain. J Mol Recognit 2017 30(12).

Pastorek L, Venit T, Hozák P: Holography microscopy as an artifact-free alternative to phase-contrast. Histochem Cell Biol 2017.

Pavkova I, Kopeckova M, Klimentova J, Schmidt M, Sheshko V, Sobol M, Zakova J, Hozak P, Stulik J: The Multiple Localized Glyceraldehyde-3-Phosphate Dehydrogenase Contributes to the Attenuation of the Francisella tularensis dsbA Deletion Mutant. Front Cell Infect Microbiol 2017 7: 503.

Rodriguez-Corona U, Pereira-Santana A, Sobol M, Rodriguez-Zapata LC, Hozak P, Castano E: Novel Ribonuclease Activity Differs between Fibrillarins from Arabidopsis thaliana. Front Plant Sci 2017 8: 1878.

Rohlenova K, Sachaphibulkij K, Stursa J, Bezawork-Geleta A, Blecha J, Endaya B, Werner L, Cerny J, Zobalova R, Goodwin J, Spacek T, Alizadeh Pesdar E, Yan B, Nguyen MN, Vondrusova M, Sobol M, Jezek P, Hozak P, Truksa J, Rohlena J, Dong LF, Neuzil J: Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2(high) Breast Cancer. Antioxid Redox Signal 2017 26(2): 84-103.

Ulicna L, Kalendova A, Kalasova I, Vacik T, Hozák P: PIP2 epigenetically represses rRNA genes transcription interacting with PHF8. Biochim Biophys Acta 2017 1863(3): 266-275.

2016

Kalasova I, Fáberová V, Kalendová A, Yildirim S, Uličná L, Venit T, Hozák P: Tools for visualization of phosphoinositides in the cell nucleus. Histochem Cell Biol 2016 145(4): 485-96.

Nebesářová J, Hozák P, Frank L, Štěpan P, Vancová M: The cutting of ultrathin sections with the thickness less than 20 nm from biological specimens embedded in resin blocks. Microsc Res Tech 2016 79(6): 512-7

Pasdar EA, Smits M, Stapelberg M, Bajzikova M, Stantic M, Goodwin J, Yan B, Stursa J, Kovarova J, Sachaphibulkij K, Bezawork-Geleta A, Sobol M, Filimonenko A, Tomasetti M, Zobalova R, Hozak P, Dong LF, Neuzil J: Correction: Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents. PLoS One 2016 11(5): e0156012.

Tomasetti M, Monaco F, Manzella N, Rohlena J, Rohlenova K, Staffolani S, Gaetani S, Ciarapica V, Amati M, Bracci M, Valentino M, Goodwin J, Nguyen M, Truksa J, Sobol M, Hozak P, Dong LF, Santarelli L, Neuzil J: MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma. Oncotarget 2016 7(24): 36338-36352.

Venit T, Kalendová A, Petr M, Dzijak R, Pastorek L, Rohožková J, Malohlava J, Hozák P: Nuclear myosin I regulates cell membrane tension. Sci Rep 2016 6: 30864.

Vrbacký M, Kovalčíková J, Chawengsaksophak K, Beck IM, Mráček T, Nůsková H, Sedmera D, Papoušek F, Kolář F, Sobol M, Hozák P, Sedlacek R, Houštěk J: Knockout of Tmem70 alters biogenesis of ATP synthase and leads to embryonal lethality in mice. Hum Mol Genet 2016.

Zhironkina OA, Kurchashova SY, Pozharskaia VA, Cherepanynets VD, Strelkova OS, Hozak P, Kireev II: Mechanisms of nuclear lamina growth in interphase. Histochem Cell Biol 2016 145(4): 419-32.

2015

Dráberová E, D'Agostino L, Caracciolo V, Sládková V, Sulimenko T, Sulimenko V, Sobol M, Maounis NF, Tzelepis E, Mahera E, Křen L, Legido A, Giordano A, Mörk S, Hozák P, Dráber P, Katsetos CD: Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma. J Neuropathol Exp Neurol 2015 74(7): 723-42.

Kitamura H, Matsumori H, Kalendova A, Hozak P, Goldberg IG, Nakao M, Saitoh N, Harata M: The actin family protein ARP6 contributes to the structure and the function of the nucleolus. Biochem Biophys Res Commun 2015 464(2): 554-60.

Kosi N, Alić I, Kolačević M, Vrsaljko N, Jovanov Milošević N, Sobol M, Philimonenko A, Hozák P, Gajović S, Pochet R, Mitrečić D: Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain. Brain Res 2015 1597: 65-76.

Loizeau D, Jurkiewicz P, Aydogan G, Philimonenko AA, Mahfoudhi S, Hozák P, Maroto A, Couthon-Gourvès H, Jaffrès PA, Deschamps L, Giamarchi P, Hof M: Biophysical properties of cationic lipophosphoramidates: Vesicle morphology, bilayer hydration and dynamics. Colloids Surf B Biointerfaces 2015 136: 192-200.

Loza-Muller L, Rodríguez-Corona U, Sobol M, Rodríguez-Zapata LC, Hozak P, Castano E: Fibrillarin methylates H2A in RNA polymerase I trans-active promoters in Brassica oleracea. Front Plant Sci 2015 6: 976.

Marášek P, Dzijak R, Studenyak I, Fišerová J, Uličná L, Novák P, Hozák P: Paxillin-dependent regulation of IGF2 and H19 gene cluster expression. J Cell Sci 2015 128(16): 3106-16

Margaryan H, Dorosh A, Capkova J, Manaskova-Postlerova P, Philimonenko A, Hozak P, Peknicova J: Characterization and possible function of glyceraldehyde-3-phosphate dehydrogenase-spermatogenic protein GAPDHS in mammalian sperm. Reprod Biol Endocrinol 2015 13: 15.

Pasdar EA, Smits M, Stapelberg M, Bajzikova M, Stantic M, Goodwin J, Yan B, Stursa J, Kovarova J, Sachaphibulkij K, Bezawork-Geleta A, Sobol M, Filimonenko A, Tomasetti M, Zobalova R, Hozak P, Dong LF, Neuzil J: Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents. PLoS One 2015 10(5): e0119549.

Rodriguez-Corona U, Sobol M, Rodriguez-Zapata LC, Hozak P, Castano E: Fibrillarin from Archaea to human. Biol Cell 2015 107(6): 159-74.

Tan AS, Baty JW, Dong LF, Bezawork-Geleta A, Endaya B, Goodwin J, Bajzikova M, Kovarova J, Peterka M, Yan B, Pesdar EA, Sobol M, Filimonenko A, Stuart S, Vondrusova M, Kluckova K, Sachaphibulkij K, Rohlena J, Hozak P, Truksa J, Eccles D, Haupt LM, Griffiths LR, Neuzil J, Berridge MV: Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab 2015 21(1): 81-94.

2014

Härtlová A, Link M, Balounová J, Benešová M, Resch U, Strasková A, Sobol M, Philimonenko A, Hozák P, Krocová Z, Gekara N, Filipp D, Stulík J: Quantitative Proteomics Analysis of Macrophage-derived Lipid Rafts Reveals Induction of Autophagy Pathway at the Early Time of Francisella tularensis LVS infection. J Proteome Res 2014 13(2): 796-804.

Kalendová A, Kalasová I, Yamazaki S, Uličná L, Harata M, Hozák P: Nuclear actin filaments recruit cofilin and actin-related protein 3, and their formation is connected with a mitotic block. Histochem Cell Biol 2014 142(2): 139-52.

Philimonenko VV, Philimonenko AA, Šloufová I, Hrubý M, Novotný F, Halbhuber Z, Krivjanská M, Nebesářová J, Šlouf M, Hozák P: Simultaneous detection of multiple targets for ultrastructural immunocytochemistry. Histochem Cell Biol 2014 141(3): 229-39.

2013

Roth J, Debbage P, Hozák P: In focus in Prague: intermediate filaments. Histochem Cell Biol 2013 140(1): 1-2.

Sobol M, Yildirim S, Philimonenko VV, Marášek P, Castaño E, Hozák P: UBF complexes with phosphatidylinositol 4,5-bisphosphate in nucleolar organizer regions regardless of ongoing RNA polymerase I activity. Nucleus 2013 4(6): 478-86.

Venit T, Dzijak R, Kalendová A, Kahle M, Rohožková J, Schmidt V, Rülicke T, Rathkolb B, Hans W, Bohla A, Eickelberg O, Stoeger T, Wolf E, Yildirim AÖ, Gailus-Durner V, Fuchs H, de Angelis MH, Hozák P: Mouse nuclear Myosin I knock-out shows interchangeability and redundancy of Myosin isoforms in the cell nucleus. PLoS One 2013 8(4): e61406

Yildirim S, Castano E, Sobol M, Philimonenko VV, Dzijak R, Venit T, Hozák P: Involvement of phosphatidylinositol 4,5-bisphosphate in RNA polymerase I transcription. J Cell Sci 2013 126(Pt 12): 2730-9.

Team

Prof., RNDr.
Pavel Hozák, DrSc.

Head of Group Structures of the Cell Nucleus in Gene Expression

pavel.hozak@img.cas.cz
+420325873104