Epigenetics and Chromatin

PROFILE

In eukaryotes, DNA is compacted into chromatin, of which the basic unit is the nucleosome. Nucleosomes are comprised of two copies of each of four proteins histones wrapped by 147 base pairs of DNA. Compacting DNA allows the molecule to fit into cells in an orderly fashion, but makes DNA less accessible to cellular machinery such as transcription factors. To overcome this difficulty, histone post-translational modifications and histone variants maintain chromatin in a dynamic state regulating its accessibility. Thus, genes that are required for cellular processes can be expressed or repressed at the appropriate time. Our research focuses on understanding the mechanisms by which chromatin and its modifications regulate cellular processes. We have three main areas of investigation: the analysis of post-translational modifications of histones before they are incorporated in the chromatin, the role of the viral chromatin in the replication of the Hepatitis B Virus, and the characterization of the epigenetic modifications during the differentiation of T lymphocytes.

LAB MEMBERS

Research Head: Alejandra Loyola

Doctoral Students: Francisca Alvarez • Cristian Doñas • Sergio Hernández • Juan Hormazábal • Francisca Muñoz • Francisco Saavedra

Undergraduate Students: Pilar Castillo • Claudia Espinoza • Daniel Garrido • Sebastián Marty • Karla Veas

Research Assistants: Olivia Farias • Francisco Osorio

COLLABORATIONS

National Collaborations:
• Dr. Iván Alfaro (Universidad de Playa Ancha)
• Dr. Rodrigo Pacheco (Fundación Ciencia & Vida)
• Dr. Mario Rosemblatt (Fundación Ciencia & Vida)

International Collaborations:
• Dr. Genevieve Almouzni (Institut Curie, Paris, France)
• Dr. Danny Reinberg (Howard Hughes Medical Institute / NYU Langone School of Medicine, New York, USA)
• Dr. Axel Imhof (Ludwig-Maximilians Universität München, Munich, Germany)
• Dr. Eric Campos (University of Toronto, Toronto, Canada)

SELECTED PUBLICATIONS

  • Doñas C., Carrasco M., Fritz M., Prado C., Tejón G., Osorio-Barrios F., Manríquez V., Pacheco R., Reyes P., Bono M. R., Loyola A., Rosemblatt M. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on dendritic cells. J. Autoimmun. 75:105-117. doi: 10.1016/j.jaut.2016.07.011 (2016) | | ABSTRACT
  • Alarcón V., Hernández S., Rubio L., Alvarez F., Flores Y., Varas-Godoy M., De Ferrari G. V., Kann M., Villanueva R. A., Loyola A. The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state. Sci. Rep. May 13; 6:25901. doi: 10.1038/srep25901 (2016) | | ABSTRACT
  • Hernández S., Jiménez G., Alarcón V., Prieto C., Muñoz F., Riquelme C., Venegas M., Brahm J., Loyola A., Villanueva R. A. Replication of a chronic hepatitis B virus genotype F1b construct. Arch. Virol. 161(3): 583 (2016) | | ABSTRACT
  • Rivera C., Saavedra F., Alvarez F., Díaz-Celis C., Ugalde V., Li J., Forné I., Gurard-Levin Z. A., Almouzni G., Imhof A., Loyola A. Methylation of histone H3 lysine 9 occurs during translation. Nucleic Acids Res. 43(19): 9097-9106 (2015) | | ABSTRACT
  • Ugarte G. D., Vargas M. F., Medina M. A., León P., Necuñir D., Elorza A. A., Gutiérrez S. E., Moon R. T., Loyola A., De Ferrari G. V. Wnt signaling induces transcription, spatial proximity and translocation of fusion gene partners in human hematopoietic cells. Blood 126(15): 1785 (2015) | | ABSTRACT
  • Rivera C., Gurard-Levin Z. A., Almouzni G., Loyola A. Histone lysine methylation and chromatin replication. Biochim. Biophys. Acta 1839(12):1433-1439 (2014) | | ABSTRACT
  • Doñas C., Fritz M., Manríquez V., Tejón G., Bono M. R., Loyola A., Rosemblatt M. Trichostatin A promotes the generation and suppressive functions of regulatory T cells. Clin. Dev. Immunol 2013, 679804 (2013) | PDF | ABSTRACT
  • Alvarez F., Muñoz F., Schilcher P., Imhof A., Almouzni G., Loyola A. Sequential establishment of marks on soluble histones H3 and H4. J. Biol. Chem. 20(286): 17714-17721 (2011) | PDF | ABSTRACT
  • Loyola A., Tagami H., Bonaldi T., Roche D., Quivy J. P., Imhof A., Nakatani Y., Dent S. Y. R., Almouzni G. The HP1α -CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep. 10(7): 769-775 (2009) | PDF | ABSTRACT
  • Loyola A., Almouzni G. Marking histone H3 variants: How, when and why?. Trends Biochem. Sci. 32(09): 425-433 (2007) | PDF | ABSTRACT
  • Loyola L., Bonaldi T., Roche D., Imhof A., Almouzni G. PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. Mol. Cell. 24, 309–316 (2006) | PDF | ABSTRACT
  • Loyola, A., He S., Oh S., McCafferty D. G., Reinberg D. Techniques used to study transcription on chromatin templates. Methods Enzymol., vol. 377, pp 474-499 (2004) | | ABSTRACT
  • Loyola A., Almouzni G. Histone chaperones, a supporting role in the limelight. Institut Curie/Section de Recherche 1677, 03-11 (2004) | PDF | ABSTRACT
  • Loyola A., Almouzni G. Bromodomains in living cells participate in deciphering the histone code. Trends Cell Biol. 14(6): 279-281 (2004) | PDF | ABSTRACT
  • Vaquero A., Loyola A., Reinberg D. The constantly changing face of chromatin. Sci. Aging Knowl. Environ. 2003(14): 01-16 (2003) | PDF | ABSTRACT
  • Loyola A., Huang J. Y., LeRoy G., Hu S., Wang Y-H., Donnelly R. J., Lane W. S., Lee S-C., Reinberg D. Functional analysis of the subunits of the chromatin assembly factor RSF. Mol. Cell. Biol. 23(19): 6759–6768 (2003) | PDF | ABSTRACT
  • Loyola A., Reinberg D. Histone deposition and chromatin assembly by RSF. Methods, vol 31: 96–103 (2003) | PDF | ABSTRACT
  • He S., Bauman D., Davis J. S., Loyola A., Nishioka K., Gronlund J. L., Reinberg D., Meng F., Kelleher N., McCafferty D. G. Facile synthesis of site-specifically acetylated and methylated histone proteins: Reagents for evaluation of the histone code hypothesis. PNAS 100(21): 12033-12038 (2003) | PDF | ABSTRACT
  • Loyola A., LeRoy G., Wang Y-H., Reinberg D. Reconstitution of recombinant chromatin establishes a requirement for histone-tail modifications during chromatin assembly and transcription. Genes Dev. 15(21): 2837–2851 (2001) | PDF | ABSTRACT
  • LeRoy G., Loyola A., Lane W. S., Reinberg D. Purification and characterization of a human factor that assembles and remodels chromatin. J. Biol. Chem. 275(20): 14787–14790 (2000) | PDF | ABSTRACT