DNA replication, cell division and chromatin

Group leader: Crisanto Gutierrez Armenta,
Postdoctoral Fellows: Irene Aragüez Rey, Elena Caro Bernat, Joana De Brito Lourenço Sequeira Mendes, Benedicte Desvoyes, María Fernandez Marcos,
Graduate Students: Sofia Otero Perez, Zaida Vergara Pradillo,
Technical Assistance: Mª Victoria Mora-Gil Cobo,

Research Summary

DNA replication, cell division and chromatin
Development of multicellular organisms depnds on a strict balance between cell proliferation and differentiation, where highly regulated gene expression patterns are established. Contrary to animals, plant development is a postembryonic process that frequently relies on endoreplication cycles. In addition, various differentiated cell types retain the capacity to dedifferentiate, proliferate again and take a variety of morphogenetic patterns. We are interested in understanding how such balance is established during development by studying cell division and DNA replication control, as well as the implications of chromatin dynamics. To that end, we use the model plant Arabidopsis thaliana that allows the use of molecular, cellular, genetic and genomic approaches.

We have generated a genome-wide map of DNA replication origins of Arabidopsis cultured cells and analyzed their features and the function of pre-RC components. We have also demonstrated a role of ORC1 as a transcriptional activator through a PHD motif that is not present in ORC1 of yeast or human origin and mediates interaction of ORC1 with H3K4me3. We are currently studying the contribution of this interaction to origin function. Based on our previous results on the effect of the histone chaperone CAF-1 in controlling endoreplication, we are extending these studies to other histone chaperones and H3 dynamics. The coordination between cell division and endoreplication and cell fate acquisition depends on the plant retinoblastoma-related (RBR) protein. We continue our studies of its function, both E2F-dependent and independent, in the expression of genes required for cell cycle exit.

Our long-term interest is to understand the crosstalk of cell division, chromatin and differentiation during Arabidopsis development with a special focus in understanding initiation of DNA replication, its regulation in a whole organism and the implications of the novel cellular factors that we are identifying.



Figure 1.
Model of transcriptional activation by Arabidopsis ORC1, adapted from Sanchez and Gutierrez (2009; PNAS 106, 2065-2070).

Figure 2.
Genome-wide maps of Arabidopsis DNA replication origins (light blue), ORC1 (red) and CDC6 (yelow) binding sites and ORFs (green), adapted from Costas et al., (2011, Nature Struc. Mol. Biol.).



- Caro, E., Desvoyes, B., Gutierrez, C. GTL1 keeps cell growth and nuclear ploidy under control.
EMBO J.  (Nov 27, 2012) doi: 10.1038/emboj.2012.311

- Sanchez, M. de la P., Costas, C., Sequeira-Mendes, J., Gutierrez, C. Regulating DNA replication in plants.
Cold Spring Harb. Perspect. Biol. 4:a010140 (2012)

- Manzano, C., Ramirez-Parra, E., Casimiro, I., Otero, S., Desvoyes, B., De Rybel., B., Beeckman, T., Casero, P., Gutierrez, C., del Pozo, J.C. Auxin and epigenetic regulation of SKP2B, an F-box that represses lateral root formation.
Plant Physiol. 160, 749-762 (2012)   

- Stroud, H. +, Otero, S.+, Desvoyes, B., Ramirez-Parra, E., Jacobsen, S.E., Gutierrez, C. Genome-wide analysis of histone H3.1 and H3.3 variants in Arabidopsis thaliana.
Proc. Natl. Acad. Sci. USA 109, 5370-5375 (2012)    + Co-first authors


- Sanmartin, M., Sauer, M., Muñoz, A., Zouhar, J., Ordoñez, A., van de Ven, W.T.G., Caro, E., Sanchez, M.P., Raikhel, N., Gutierrez, C., Sanchez-Serrano.J.J., Rojo, E. “A molecular switch for initiating cell differentiation in Arabidopsis”.
Curr. Biol. 21, 999-1008 (2011)   

- Costas, C.+, Sanchez, M.P.+, Sequeira-Mendes, J.+, Gutierrez, C. “Progress in DNA replication control”.
Plant Sci.  181, 203-209 (2011) + Co-first authors.

- Costas, C.+, Sanchez, M.P.+, Stroud, H.+, Yu, Y., Oliveros, J.C., Feng, S., Benguria, A., López-Vidriero, I., Zhang, X., Solano, R., Jacobsen, S.E., Gutierrez, C. “Genome-wide mapping of Arabidopsis origins of DNA replication and their associated epigenetic marks”.
Nat. Struct. Mol. Biol. 18, 395-400 (2011) + Co-first authors.

- Lario, L., Ramirez-Parra, E., Gutierrez, C., Casati, P., Spampinato, C. “Regulation of plant MSH2 and MSH6 genes in the UV-B induced DNA damage response”. J. Exp. Bot. 62, 2925-2937 (2011).

- Desvoyes, B., Costas, C., Gutierrez, C. A chromatin perspective of cell cycle progression. Biochim. Biophys. Acta 1809, 379-387 (2011) doi: 10.1016/j.bbagrm.2011.03.005)


- Desvoyes, B., Sanchez, M.P., Ramirez-Parra, E. "Impact of nucleosome dynamics and histone modifications on cell proliferation during Arabidopsis development".  Heredity 105, 80-91 (2010).

- Jacob, Y.*, Stroud, H.*, LeBlanc, C., Feng, S., Zhou, L., Caro, E., Hassel, C., Gutierrez, C., Michaels, S.D., Jacobsen, S.E. "Two histone H3 lysine methyltransferases, ATXR5 and ATXR6, regulate DNA replication in heterochromatin". Nature 466, 987-991 (2010).


- Sanchez, M.P., Gutierrez, C. "Novel insights into the plant histone code: lessons from ORC1". Epigenetics 4, 205-208 (2009).

- Sanchez, M.P., Gutierrez, C. “Arabidopsis ORC1 is a novel PHD-containing H3K4me3 effector that regulates transcription”. Proc. Natl Acad. Sci USA 106, 2065-2070 (2009).

- Gutierrez, C. "The Arabidopsis cell division cycle". doi: 10.1199/tab.0120 (2009) In: The Arabidopsis Book, Rockville, MD: American Society of Plant Biologists. http://www.aspb.org/publications/arabidopsis/ 

- Gutierrez, C., Martinez-Salas, E. "Replication of viruses infecting eukaryotes". Article A21993
In: Encyclopedia of Life Sciences, London, Nature Publishing Group. http://www.els.net        


-    Jurado, S., Diaz-Trivino, S., Abraham, Z, Manzano, C., Gutierrez, C., del Pozo, J.C. “SKP2A protein, an F-box that regulates cell division, is degraded via de ubiquitin pathway”. Plant J. 53, 828-841 (2008).

-    Caro, E., Desvoyes, B., Ramirez-Parra, E., Sanchez, M.P., Gutierrez, C. “Endoreplication control during plant development”. In: Eukaryotic cell cycle. J. Bryant & D. Francis (Eds.), pp. 167-187. Garland Science, Taylor & Francis Group (United Kingdom). (2008).

-    Najera-Martinez, M., Ramirez-Parra, E., Vazquez-Ramos, J., Gutierrez, C., Plasencia, J. “Cloning and molecular characterisation of the maize retinoblastoma gene (ZmRBR2)”. Plant Sci. 175, 685-693. (2008).

-    Jurado, S., Diaz-Trivino, S., Abraham, Z., Manzano, C., Gutierrez, C., del Pozo, J.C. “SKP2A protein, an F-box that regulates cell division, is degraded via the ubiquitin pathway”. Plant Sign. Behav. 3, 810-812 (2008).

-    Sanchez, M.P., Caro, E., Desvoyes, B., Ramirez-Parra, E., Gutierrez, C. “Chromatin dynamics during the plant cell cycle”. Semin. Cell Dev. Biol. 19, 537-546. (2008)

-    Ramirez-Parra, E., Gutierrez, C. “Role of E2F transcription factors in plant cell physiology and development”. In: Control of cellular physiology by E2F transcription factors, K. Yoshida, Ed., pp 1-15. Research Signpost, (India). (2008).


-    del Pozo, J.C., Diaz-Triviño, S., Cisneros, N., Gutierrez, C. “The E2FC-DPB transcription factor controls cell division, endoreplication and lateral root formation in a SCFSKP2A- dependent manner” Plant Sign. Behav. 2, 273-274 (2007)

-    Ramirez-Parra, E., del Pozo, J.C., Desvoyes, B., Sanchez, M.P., Gutierrez, C. “E2F-DP transcription factors” In: Cell Cycle Control and Plant Development, D. Inzé, Ed. pp. 138-162, Blackwell Publishing, Oxford (2007). Annu. Plant. Rev. 32, 138-162 (2007)

-    Gutierrez, C. “Coordination of cell division and differentiation” In: Cell Division Control in Plants, D.P.S. Verma, Z. Hong, Eds. pp. 377-393. Springer-Verlag, Heidelberg (2007)

-    Ramirez-Parra, E., Gutierrez, C. “E2F regulates FASCIATA1, a chromatin assembly gene whose loss switches on the endocycle and activates gene expression by changing the epigenetic status”. Plant Physiol. 144, 105-120. (2007)

-    Caro, E., Castellano, M.M., Gutierrez, C. “A chromatin link that couples cell division to root epidermis patterning in Arabidopsis”.
447, 213-217. (2007)

-    Caro, E. Gutierrez, C. “A  green GEM: intriguing analogies with animal geminin”. Trends Cell Biol. 17, 580-585. (2007).

-    Caro, E., Castellano, M.M., Gutierrez, C. “) Coordination of cell division and cell fate decisions”. Plant Sign. Behav. 2, 494-495. (2007).

-    Ramirez-Parra, E., Gutierrez, C. “The many faces of chromatin assembly factor 1”. Trends Plant Sci. 12, 570-576. (2007).


-    Desvoyes, B., Ramirez-Parra, E., Xie, Q., Chua, N.-H., Gutierrez, C. “Cell type-specific role of the retinoblastoma/E2F pathway during Arabidopsis leaf development” Plant Physiol. 140, 67-80 (2006)

-    Gutierrez, C. “Replication and expression of DNA viruses”. In: Handbook of Plant Virology, J.A. Khan, J. Dijstra, Eds. Haworth Press, pp. 75-91. New York (USA) (2006).

-    Gutierrez, C. “Plant cells and viruses”. In: DNA replication and human disease (ed. M.L. DePamphilis), pp. 257-272.  Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. (2006)

-    del Pozo, J.C., Diaz-Triviño, S., Cisneros, N., Gutierrez, C. “The balance between cell division and endoreplication depends on E2Fc-DPb, transcription factors regulated by the ubiquitin-SCFSKP2A pathway” Plant Cell 18, 2224-2235 (2006).


-    del Pozo, J.C., Lopez-Matas, M.A., Elena Ramirez-Parra, E., Gutierrez, C. “Hormonal control of the cell cycle”  Physiol. Plant. 123, 173-183 (2005)

-    Ramirez-Parra, E., Desvoyes, B., Gutierrez, C. “Balance between cell división and differentiation during plant development”
Int. J. Dev. Biol. 49, 467-477 (2005)

-    Gutierrez, C. “Coupling cell proliferation and development in plants” Nature Cell Biol. 7, 535-541 (2005)

-    Diaz-Trivino, S., Castellano, M.M., Sanchez, M.P., Ramirez-Parra, E., Desvoyes, B., Gutierrez, C. “The genes encoding Arabidopsis ORC subunits are E2F targets and the two ORC1 genes are differently expressed in proliferating and endoreplicating cells”. Nucleic Acids Res. 33, 5404-5414 (2005).


   Premio de Investigación en Biología Molecular de la Fundación Carmen y Severo Ochoa (2008).                 

Doctoral Theses

Elena Caro Bernat (2008) Functional network of GEM, a novel regulator of Arabidopsis root development. Mención Europea.

Pablo Castillejo Pons (2008) Dinámica de ORC6 durante el ciclo celular en Arabidopsis thaliana.

Other activities

Member Editorial Board: EMBO J., EMBO reports, J. Gen. Virol.

Editor, Plant J. (2010)

Organizer: Cantoblanco Workshop Chromatin at the nexus of cell proliferation and differentiation (2008), with B. Scheres, U.Grossniklaus

Co-organizer: 2nd EMBO Conference on Plant Molecular Biology "Frontiers of Plant Research", Cadiz, Spain, May 6-9, 2009, with M. Pages, J. Paz-Ares, P. Puigdomenech, R. Serrano.

C/Nicolás Cabrera 1 Campus de la Universidad Autónoma de Madrid.. 28049-Madrid .
Teléfono: +34-911964401 , Fax: +34-911964420 , e-mail: institucional@cbm.uam.es