Structural and functional regulation of Arabidopsis thaliana telomeres

Current research interests:

Telomeres guarantee the replication of chromosome ends, prevent genome instability and influence relevant biological processes like aging and cancer. Studies performed in different model systems have revealed that telomeres function requieres the integrity of heterochromatin. We have previously found that whereas Arabidopsis italiana telomeres are not heterochromatic, subtelomeres in Arabidopsis organize as heterochromatin. We have also found that human telomeres are not heterochromatic either in most commonly studied human cell lines. Since heterochromatin influences telomeres function in both, human and Arabidopsis, we have hypothesized that subtelomeric heterochromatin plays an important role in telomeres biology. We are currently studying the influence of the chromatin organization of telomeric regions, including telomeres and subtelomeres, on the biology of telomeres.

 Miguel A. Vega-Palas CV:

Miguel A. Vega-Palas, Scientific Researcher (CSIC)
BA 1986 Biology, University of Seville, Seville, Spain 
PhD 1991 Biology, University of Seville, Seville, Spain 

Current address:

Instituto de Bioquímica Vegetal y Fotosíntesis
Centro de Investigaciones Isla de la Cartuja
c/ Américo Vespucio nº 49
41092 Sevilla
Spain
E-mail: vega-palas@ibvf.csic.es 
Phone: 34-954-489591
Fax: 34-954-460065

 Appointments:

(1987-1990) Predoctoral Researcher. University of Seville, Spain.
(1991-1992) Postdoctoral Researcher. Spanish Scientific Council (CSIC), Spain.
(1992-1995) Postdoctoral Researcher. University of Florida, USA.
(1995-1996) Postdoctoral Researcher. University of Rome, Italy.
(1997-1998) Teaching Assistant. University of Seville, Spain.
(1999) Postdoctoral Researcher. UCLA, Los Angeles, USA.
(1999-2001) Postdoctoral Researcher. Spanish Scientific Council (CSIC), Spain.
(2001-2002) Associated Professor. University of Seville, Spain.
(2003 to date) Permanent position as Researcher. Institute of Vegetal Biochemistry and Photosynthesis (IBVF), CSIC, Spain.

Research highlights:

 Dr. Vega-Palas has worked with four different model systems: cyanobacteria, yeast, Arabidopsis thaliana and humans.

In cyanobacteria, Dr. Vega-Palas collaborated in the identification of the NtcA protein (1). NtcA is a global regulator of nitrogen assimilation processes, including the differentiation of heterocysts. Heterocysts are specialized cells present in filamentous cyanobacteria that fix atmospheric nitrogen using the energy supplied by photosynthesis. Since cyanobacteria represent a high proportion of the seas productivity, they contribute significantly to the production of atmospheric oxygen, with the consequent removal of CO2

In yeasts, he collaborated in the identification of telomeric silencing in a natural context (2). Previously, subtelomeric heterochromatin had been found to silence the expression of genes introduced artificially in subtelomeric regions (a phenomenon called TPE). In this study, they showed that the Ty5-1 retrotransposon, which is naturally found in subtelomeric regions, undergoes TPE. This study contributed to demonstrate that eukaryotic heterochromatin controls mobile elements.

In Arabidopsis, Dr. Vega-Palas focuses on the study of the chromatin organization and function of telomeres. The chromatin organization of telomeres play a relevant role in telomeres function and cell proliferation. Therefore, its study is becoming an issue of major interest. The epigenetic modifications of telomeres are usually analyzed by microscopy or by chromatin immunoprecipitation (ChIP). However, these analyses could be challenged by subtelomeres and/or interstitial telomeric sequences (ITSs). Whereas telomeres and subtelomeres cannot be differentiated by microscopy techniques, telomeres and ITSs might not be differentiated in ChIP analyses. In addition, ChIP analyses of telomeres should be properly controlled. Hence, studies focusing on the epigenetic modifications of telomeres have to be carefully designed and interpreted. Dr. Vega-Palas’s group has designed several techniques that allow the study of telomeres independently of ITSs and subtelomeric regions. With the use of these techniques they have found that Arabidopsis telomeres are not heterochromatic. In turn, subtelomeric regions and ITSs exhibit heterochromatic features (3-6). In addition, Dr. Vega-Pala’s lab has set up a method to determine the length of Arabidopsis telomeres by PCR (7). Since this method requires low amounts of biological material, it could allow the study of telomere length in specific cell types.

In humans, Dr. Vega-Palas’s group has studied the epigenetic nature of telomeres by analyzing massive sequencing data. They have found that human telomeres are not heterochromatic in most commonly studied human cells (8). Thus, human and Arabidopsis telomeres have a bimodal chromatin organization with non-heterochromatic telomeres and subtelomeres that fold into heterochromatin. Dr. Vega-Palas’s lab has proposed a standard method to analyze the epigenetic features of human telomeres. This method is based on the use of the ChIP technique followed by hybridization or sequencing. Comprehensive studies of telomeric chromatin organization and function might help defining the rationale for combining epigenetic drugs among them and with other oncogenic drugs for cancer treatment. Hence, the analysis of telomere epigenetics could help designing precise epigenetic therapies for specific cancer types (9,10).

References:

1.Vega-Palas, M. A., Flores E. and Herrero A. (1992). NtcA, a novel regulator from the cyanobacterium Synechococcus that belongs to the Crp family of bacterial regulators. Molecular Microbiology 6, 1853-1859.

2.Vega-Palas, M. A., Venditti, S. and Di Mauro E. (1997). Telomeric transcriptional silencing in a natural context. Nature Genetics 15, 232-233.

3. Vaquero-Sedas, M., Gámez-Arjona, F. and Vega-Palas, M. (2011) Arabidopsis thaliana telomeres exhibit euchromatic features. Nucleic Acids Research 39, 2007-2017.

4. Vaquero-Sedas, M., Luo, C. and Vega-Palas, M. (2012) Analysis of the epigenetic status of telomeres by using ChIP-seq data. Nucleic Acids Research 40, e163.

5. Vaquero-Sedas, M. and Vega-Palas, M. (2013) Differential association of Arabidopsis telomeres and centromeres with histone H3 variants. Scientific Reports 3, 1202.

6. Vega-Vaquero, A., Bonora, G., Morselli, M., Vaquero-Sedas, M., Rubbi, L., Pellegrini, M. and Vega-Palas, M.A. (2016) Novel features of telomere biology revealed by the absence of telomeric DNA methylation. Genome Research 26, 1047-1056.

7. Vaquero-Sedas, M. and Vega-Palas, M. (2014) Determination of Arabidopsis thaliana telomere length by PCR. Scientific Reports 4.

8. Cubiles, M., Barroso, S., Vaquero-Sedas, M., Enguix, A., Aguilera A. and Miguel A. Vega-Palas, M. (2018) Epigenetic features of human telomeres. Nucleic Acids Research 46: 2347–2355.

9. Vaquero-Sedas M. and Vega-Palas, M. (2019) Assessing the epigenetic status of human telomeres. Cells 8: 1050.

10. Vaquero-Sedas, M. and Vega-Palas, M. (2019) Targeting cancer through the epigenetic features of telomeric regions. Trends in Cell Biology 29: 281-290.

Others:

-Editorial board member of Scientific Reports (2015 to date). (http://www.nature.com/srep/index.html)

-Editorial board member of Epigenetic Diagnosis & Therapy (2013-2018).(http://www.benthamscience.com/edt

-Collaboration in teaching a master course on “Epigenetics” at the University of Seville, Spain (2009-2016).

-Associated member of the Epigenesys European Network of Excellence (2013).

-Organization of the European ARABIDO-SEED trilateral network annual meeting. Seville, Spain (2007).

-Organization of the Juan March Workshop on Chromatin and DNA modification: Plant Gene Expression and Silencing, together with Drs. Alan Wolfe, Robert J. Ferl and Timothy Hall. Madrid, Spain (1998).

-Extraordinary PhD Award, University of Seville, Spain (1992).

-Extraordinary Graduation Award, University of Seville, Spain (1986).

-Sevillian Electric Company Award to the Best Academic Grades in Biology, Spain (1986).

 

Selected Publications
Type: Publications in journals
Novel features of telomere biology revealed by the absence of telomeric DNA methylation
Authors: Vega-Vaquero, A., Bonora, G., Morselli, M., Vaquero-Sedas, M.I., Rubbi, L., Pellegrini, M., Vega-Palas, M.A.
Publication Year: 2016
Pages: 1047-1056
Journal: Genome Res.
Volume: 26(8)
Type: Publications in journals
Telomeric transcriptional silencing in a natural context
Authors: Vega-Palas, M. A., Venditti, S. and Di Mauro, E.
Publication Year: 1997
Pages: 232-233
Journal: Nature Genetics
Volume: 15