DNA replication, chromatin and cell division

Research summary:

The transition to multicellularity required the acquisition of novel structures and mechanisms to coordinate cell division, acquisition of cell fates and the differentiation, and the establishment of complex regulatory networks. Our group is interested in understanding the mechanisms that control these processes and how epigenetic mechanisms affect such coordination.

To that end, we use the model plant Arabidopsis thaliana that offers us the possibility of carrying out molecular, cellular, genetic and genomic approaches. In addition, plant development, contrary to the situation in animals, is post-embryonic and occurs during the entire life of the organism. Our research is aimed at understanding fundamental questions on cell proliferation control, cellular homeostasis and genome replication in multicellular organisms.

We have developed genomic strategies to study the functional properties and molecular determinants of DNA replication origins (ORIs) in all cell types of the whole organism to determine the influence of hormonal conditions, developmental signals and the environment (Fig. 1). We found that ORI activity is compatible with multiple signatures although most of them tend to associate with chromatin states present in proximal promoters, TSS and 5’-end of genes. In addition, ORIs are enriched in the tandem arrays of GGN trinucleotides, which can for G4 structures. Our experimental approach is opening a new avenue to use mutants in the analysis of genome replication. We are combining the study of molecular determinants of ORIs with detailed analysis of the pre-RC dynamics during organ development.

Cell proliferation is crucial for organogenesis, which is determined by a strict control of gene expression patterns. We study chromatin dynamics along the cell cycle with special emphasis in two aspects: one, the regulation of cell proliferation potential, very related to the control of gene expression in G1 and G2, and the exit to differentiation, and another, related to the specific chromatin modifications in response to stress. The balance between the canonical histone H3.1 and the variant H3.3 serves to identify the cell population undergoing their last cell cycle before exit to differentiation because most of H3.1 is massively evicted in the last G2 phase (Fig. 2), which is longer in these cells.

Image

Fig. 1. Identification of DNA replication origins (ORIs) in whole developing organisms: 4 and 10 day-old Arabidopsis thaliana seedlings (left upper panel). The procedure includes the purification of single-stranded DNA of short nascent strands (SNS), conversion to double-stranded DNA and sequencing (right upper panel). Peak identification in several experimental situations allows the genome-wide mapping of ORIs (red in lower panel).  

Image

Fig. 2. Histone H3 dynamics. The canonical H3.1 (green), incorporated in every S-phase, but not the H3.3 variant (red), incorporated in a cell cycle-independent manner, is almost completely evicted in mitotic cells (red mitosis) undergoing their last division before entering the differentiation zone. Mitotic cells in previous cell divisions (yellow mitosis) contain both H3.1 and H3.3.

Image


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Casado GarcíaNadia3084658ncasado(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Desvoyes Bénédicte3084658bdesvoyes(at)cbm.csic.esDoctor FC3
Echevarria ZomeñoClara3084658cechevarria(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Emiliani Julia3084658jemiliani(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Fung UcedaJorge Alberto3084658jorge.fung(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Gómez María Sol3084658sgomez(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
González GilAnna3084658a.gonzalez(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Gutiérrez ArmentaCrisanto3084638cgutierrez(at)cbm.csic.esE. Profesores de Investigación de Organismos Públicos de Investigación
Nuñez VázquezRocío3084658rnunez(at)cbm.csic.esTitulado Medio de Actividades Tecn.y Prof.GP2 66%

Relevant publications:

  • Ocaña-Pallarès, E., Vergara, Z., Desvoyes, B., Tejada-Jimenez, M., Romero-Jurado, A., Galvan, A., Fernandez, E., Ruiz-Trillo, I., Gutierrez, C. Origin recognition complex (ORC) evolution is influenced by global gene duplication / loss patterns in eukaryotic genomes. Genome Biol. Evol. (2020, in press, GBE-191130).
  • Sequeira-Mendes, J., Vergara, Z., Peiró, R., Morata, J., Aragüez, I., Costas, C., Mendez-Giraldez, R., Casacuberta, J.M., Bastolla, U., Gutierrez, C. Differences in firing efficiency, chromatin and transcription underlie the developmental plasticity of Arabidopsis DNA replication origins. Genome Res. 29, 784–797 (2019).
  • Desvoyes, B.*,+, Sequeira-Mendes, J.*, Vergara, Z., Madeira, S., Gutierrez, C+. Sequential ChIP protocol for profiling bivalent epigenetic modifications in the same chromatin fiber (ReChIP). * shared 1st coauthorship.  Co-coresponding authors. Methods Mol. Biol. 1675, 83-97 (2017). In: Plant Chromatin Dynamics: methods and protocols. M. Bremer, C. Baroux, Eds. Springer Science.
  • Vergara, Z., Sequeira-Mendes, J., Morata, J., Hénaff, E., Peiró, R., Costas, C., Casacuberta, J.M., Gutierrez, C. Retrotransposons are specified as DNA replication origins in the gene-poor regions of Arabidopsis heterochromatin. Nucleic Acids Res. 45, 8358–8368 (2017).
  • Fernandez-Marcos, M., Desvoyes, B., Manzano, C., Liberman, L.M., Benfey, P.N., del Pozo, J.C., Gutierrez, C. Control of Arabidopsis lateral root boundaries by MYB36. New Phytol. 213, 105-112 (2017).
  • Vergara, Z., Gutierrez, C. Emerging roles of chromatin in the maintenance of genome organization and function in plants. Genome Biol. 18, 96 (2017).
  •  Gutierrez, C., Desvoyes, B., Vergara, Z., Otero, S., Sequeira-Mendes, J. Links of genome replication, transcriptional silencing and chromatin dynamics. Curr. Opin. Plant Biol. 34, 92-99 (2016).
  • Gutierrez, C. 25 years of cell cycle research: what’s ahead? Trends Plant Sci. 21, 823-833 (2016).
  • Otero, S*., Desvoyes, B.*, Peiró, R., Gutierrez, C. Histone H3 Dynamics Reveal Domains with Distinct Proliferation Potential in the Arabidopsis Root. Plant Cell 28, 1361-1371 (2016) * shared 1st coauthorship. Plant Cell 28, 1235 (2016) In Brief- Hofmann, N. Last exit to differentiation: histone variants as signspots.
  •  Sequeira-Mendes, J., Aragüez, I., Peiró, R., Zhang, X., Jacobsen, S.E., Bastolla, U., Gutierrez, C. The Functional Topography of the Arabidopsis Genome is organized in a reduced Number of linear Motifs of Chromatin states. Plant Cell 26, 2351-2366 (2014).

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: