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Lab presentation

Multipotent cells are capable either self-renew or differentiate. This process is regulated by interactions between transcription factors, signalling proteins and epigenetic factors. Our group is focused on understanding the role of epigenetic regulators in gene transcription during development.

We use as main experimental model gene induction and silencing that take place during neurogenesis. Our work will help to understand the molecular basis of chromatin function during the development as well as in pathological processes, helping to identify new therapeutic targets.

Projects

Research Lines:

  • The role of histone methylation during neurogenesis and cell fate using chick embryo neural tube.

Neural differentiation requires general changes in gene expression in which epigenetic changes are involved. Our work has allowed to identify several signalling pathways that cooperate with the enzymes responsible of H3K27me3 to control neurogenesis. Our goal is to describe the molecular mechanisms responsible of this cooperation (Akizu et al., 2010).

  • Epigenetic defects in mental retardation. Role of histone demethylase PHF8.

A very high number of genes mutated in mental retardation encode regulators of chromatin structure. One of these genes is PHF8, a histone demethylase enzyme. The PFH8 function and the molecular mechanisms responsible for it role in mental retardation are not clearly established. In the laboratory we are interested in establishing the role of PHF8 in vivo.

  • Genome architecture contribution to cell fate determination.

Lab people

Principal investigator

Graduated in pharmacology from the Santiago de Compostela University. Marian
Martínez-Balbás obtained her PhD at the Polytechnic University of Barcelona studying
DNA and chromatin structure. She was a postdoctoral Fellow at the NIH (USA) where
she focused on chromatin remodeling and dynamics at Dr C Wu’s laboratory. She then
moved to Cambridge (UK) to the J Gurdon Institute (to the group of Dr T Kouzarides) to
study the contribution of epigenetics mechanisms to cell cycle progression, cell
proliferation and development.

In 2000 she got a permanent CSIC position at the IBMB to start a new group. Her research investigation is focused on understanding the role of several chromatin regulators controlling the transcriptional program during development in a cell-type specific manner.

Her group analyzes different aspects of chromatin dynamics during neurogenesis using in vitro (neural stem cells) and in vivo models (chicken neural tube) in physiological and pathological conditions, focusing in the role of epigenetics in intellectual disability.

Past students

Selected publications

Pappa S, Padilla N, Iacobucci S, Vicioso M, Álvarez de la Campa E, Navarro C, Marcos E, de la Cruz X, Martínez-Balbás MA. 2019. PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors. Proc Natl Acad Sci U S A;116, 19464-19473. IF: 9.58


Fueyo R, Iacobucci S, Pappa S, Estarás C, Lois S, Vicioso-Mantis M, Navarro C, Cruz-Molina S, Reyes JC, Rada-Iglesias Á, de la Cruz X, Martínez-Balbás M.A. 2018. Lineage specific transcriptio factors and epigenetic regulators mediate TGFb-dependent enhancer activation. Nucleic Acids Research. 46,3351-3365. IF:11,14


Le Dréau G, Escalona R, Fueyo R, Herrera A, Martínez JD, Usieto S, Menendez A, Pons S, Martinez-Balbas MA, Marti. 2018 E proteins sharpen neurogenesis by modulating proneural bHLH transcription factors activity in an E-box- dependent manner. Elife. pii: e37267. IF: 7,6

All publications

Fueyo R, Iacobucci S, Pappa S, Estarás C, Lois S, Vicioso-Mantis M, Navarro C, Cruz-Molina S, Reyes JC, Rada-Iglesias Á, de la Cruz X, Martínez-Balbás M.A. Lineage specific transcriptio factors and epigenetic regulators mediate TGFb-dependent enhancer activation. 2018. Nucleic Acids Research. 46, 3351-3365. https://www.ncbi.nlm.nih.gov/pubmed/29438503.


Asensio-Juan, E., Fueyo, R., Pappa, E., Iacobucci, S., Badosa, C., Lois,  S., Balada, M., Bosch-Presegué, L., Vaquero, A., Gutiérrez, S., Caelles, C., Gallego, C., de la Cruz, X., and Martínez-Balbás, M.A. The histone demethylase PHF8 is a molecular safeguard  of the IFNγ response2017Nucleic Acids Research,45, 3800-3811. https://doi.org/10.1093/nar/gkw1346


Sánchez-Cid L, Pons M, Lozano JJ, Rubio N, Guerra-Rebollo M, Soriano A, Paris-Coderch L, Segura MF, Fueyo R, Arguimbau J, Zodda E, Bermudo R, Alonso I, Caparrós X, Cascante M, Rafii A, Kang Y, Martínez-Balbás M, Weiss SJ, Blanco J, Muñoz M, Fernández PL, Thomson TM. MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells.2017. Oncotarget.8, 83384-83406. https://www.ncbi.nlm.nih.gov/pubmed/29137351


Akizu, N.,  and Martínez-Balbás, M.A. EZH2 orchestrates apicobasal polarity and neuroepithelial cell renewal2016Neurogenesis.17 Nov 2016. Review. http://dx.doi.org/10.1080/23262133.2016.1250034.


Akizu, N.,  García, MA., Estarás, C., Fueyo R., de la Cruz, X., and Martínez-Balbás, M.A.EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21. 2016. The Open Biology Journal4, 150227. http://rsob.royalsocietypublishing.org/content/royopenbio/6/4/150227.full.pdf


Lysine demethylases: structure, function and disfunction”María Alejandra García, Raquel Fueyo, and Marian A. Martínez-Balbás. 2016″Chromatin signaling“. Editorial: Elsevier. Editores: O. Binda y M.E. Fernández-Zapico. Book chapter


Fueyo, R., García, M.A. and Martínez-Balbás, M.A.Jumonji family histone demethylases in neural development. 2015. Cell and Tissue Research.,359, 87-98. Review

http://link.springer.com/article/10.1007%2Fs00441-014-1924-7


Petazzi, P.,* Akizu, N.,*  García, M.A., Estarás, C., Martinez de Paz, A.,  Rodriguez-Paredes, M., Martínez-Balbás, M.A., Huertas, D., and Esteller, M. Fine-tuning of MeCP2 expression is essential for proper nervous system development. 2014. Neurobiology of Disease.67:49-56.*Equally contributing authors.  https://www.ncbi.nlm.nih.gov/pubmed/24657916


Sánchez-Molina, S., Estarás, C., Oliva, J.L., Akizu, N., Asensio-Juan, E., Rojas, J.M. and Martínez-Balbás, M.A.Regulation of CBP and Tip60 coordinates histone acetylation at local and global level during Ras induced transformation. 2014. Carcinogenesis,35: 2194- 2202.

http://www.ncbi.nlm.nih.gov/pubmed/24853677


Estarás, C., Fueyo, R., Akizu, N.,  Beltrán S., and Martínez-Balbás, M.A.RNA polymerase progression through H3K27me3-enriched gene bodies require JMJD3 histone demethylase. 2013. Molecular Cell Biology, 24: 351-360- Highligted in MBC

http://www.molbiolcell.org/content/24/3/351.full.pdf+html?with-ds=yes


Vidal-Laliena, M., Gallastegui, E., Mateo, F., Martínez-Balbás, MA.,Pujol, MJ., Bachs, O. HDAC3 regulates cyclin A stability. 2013. J. Biol. Chemistry ,288, 21096-21104.

https://www.ncbi.nlm.nih.gov/pubmed/23760262


Perez-Luna M, Aguasca M, Perearnau A, Serratosa J, Martínez-Balbás MA, Pujol MJand Bachs O.  PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor Regulation of p27Kip1. 2012. Nucleic Acid Research, 40, 6520-6533.

https://www.ncbi.nlm.nih.gov/pubmed/22547391


Celià T, Meca-Cortés O, Martínez-Paz A, Mateo F, Ulloa C, Rubio N, Arnal A,Estarás C, Lozano JJ,  Bermudo R,  García de Herreros A, Martínez-Balbás MA, Millà J, Vilella R, Gomis R, Blanco  Fernández PL and Thomson TM. Epithelial-mesenchymal transition can suppress major attributes of epithelial tumor-initiating cells. 2012. Journal of Clinical Investigation,122, 1849-1868. http://www.jci.org/articles/view/59218/pdf


Estarás, C., Akizu, N.,  García, M.A., de la Cruz, X., and Martínez-Balbás, M.A.Genome-wide analysis reveals that Smad3 and JMJD3 HDM co-activate the neural developmental program.2012. Development.139, 2681-2691. http://dev.biologists.org/content/139/15/2681.full.pdf+html


Asensio-Juan, E. Gallego, C. and Martínez-Balbás, M.A.Histone demethylase PHF8 is essential for cytoskeleton dynamics.2012. Nucleic Acis Research,40, 9429-9440.

http://nar.oxfordjournals.org/content/40/19/9429.full.pdf+html

Project funding

ONGOING RESEARCH GRANTS 

Control epigenético de la neurogénesis: Papel de las desmetilasas de histonas JMJD3 y PHF8. BFU2012-34261:

  • Spanish Ministry for Science and Education
  • From: 12/2012 To: 12/2015
  • PI: Marian Martínez-Balbás

Defectos epigenéticos asociados al retraso mental

  • Jérôme Lejeune Fondation
  • From: 9/09/2012 To: 9/09/2014
  • PI: Marian Martínez-Balbás

Defectos epigenéticos asociados al retraso mental. 09 0210:

  • La Marató de TV3 Fondation.
  • From: 19/11/2009 To: 19/11/2012
  • PI: Marian Martínez-Balbás

Genomica estructural i aplicada SRG2009:

  • AGAUR. Generalitat de Catalunya.
  • From: 12/2009 To: 12/2014
  • Coordinator: Joaquín Roca

Mecanismos epigenéticos implicados en la proliferación y diferenciación celulares: papel de la metilación/demetilación de las histonas. BFU2009-11144:

  • Spanish Ministry for Science and Education.
  • From: 12/2009 To: 12/2012
  • PI: Marian Martínez-Balbás

COMPLETED RESEARCH GRANTS 

Mecanismos epigenéticos implicados en la proliferación y diferenciación celulares: papel de las modificaciones de las histonas BFU2006-01493

  • Spanish Ministry for Science and Education
  • From: 1/10/2006 To: 30/09/2009
  • PI: Marian Martínez-Balbás

Epigenética: mecanismos y enfermedad. Consolider Ingenio. CSD2006-00049:

  • Spanish Ministry for Science and Education
  • From 11/2006 To: 11/2011
  • Coordinator: Miguel Beato Rosal PI: Marian Martínez-Balbás

Análisis estructural y funcional de la cromatina:

  • AGAUR. Generalitat de Catalunya.
  • From: 1/1/2006 To: 1/1/2008
  • Coordinator: Ferrán Azorín Marín PI: Marian Martínez-Balbás

Estudio del papel de la acetilación en el control de la proliferación y del ciclo celular. SAF2005-01285:

  • Spanish Ministry for Science and Education
  • From: 12/2005 To: 12/2006
  • PI: Marian Martínez-Balbás

Genómica estructural: aplicación a proteínas y complejos proteicos relacionados. GEN2003-20642:

  • Spanish Ministry for Science and Education
  • From: 1/9/2004 To:1/9/2007
  • Coordinator: Miquel Coll PI: Marian Martínez-Balbás

Análisis de la función de la acetilación en el control del ciclo celular y en la transformación inducida por los oncogenes ras y antígeno T. SAF2002-00741:

  • Spanish Ministry for Science and Education
  • From: 12/2002 To: 12/2005
  • PI: Marian Martínez-Balbás

Control de la expresión génica mediante procesos de acetilación. PB98-0468:

  • Spanish Ministry for Science and Education
  • From: 1/12/1999 To 1/12/2002
  • PI: Marian Martínez-Balbás

Vacancies/Jobs

PREDOCTORAL POSITION IN EPIGENETICS 

PREDOCTORAL POSITION IN EPIGENETICS A predoctoral position is available to work on epigenetics and neurogenesis.…

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OFERTA DE CONTRATO PREDOCTORAL 

OFERTA DE CONTRATO PREDOCTORAL Se ofrece contrato predoctoral para trabajar en el Instituto de Biología…

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