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

Research Assistants: Tatiana Cruces • Claudia Espinoza • Danitza Silva

Post-doctoral Fellows: Francisco Saavedra • Simon Beard • Jose Manuel Jimenez

COLLABORATIONS

National Collaborations:
• Dr. Iván Alfaro (Universidad del Desarrollo)
• Dra. Andrea Calixto (Universidad Mayor)
• Dr. Rodrigo Pacheco (Fundación Ciencia & Vida)
• Dra. Raquel Quatrini (Fundación Ciencia & Vida)
• Dr. Mario Rosemblatt (Fundación Ciencia & Vida)
• Dr. Rodrigo Villanueva (Fundación Ciencia & Vida)

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

FORMER LAB MEMBERS

Juan Hormazábal (Former Ph.D. student, 2016-2020)

Pilar Castillo (Former undergraduate student, 2015-2019)

Rodrigo Flores (Former post-doctoral fellow, 2018-2019)

Francisca Álvarez Astudillo (Former undergraduate student and Ph.D. student, 2009-2019)
Post-doctoral fellow at Universidad San Sebastian, Chile

Pía Vidal (Former post-doctoral fellow, 2018-2019)
Assistant professor at Universidad Catolica de la Santisima Concepcion

Francisca Muñoz Garrido (Former undergraduate student and Ph.D. student, 2009-2018)

Sebastián Marty Lombardi (Former undergraduate student, 2015-2017)
AG Siemens, Pharmakologisches Institut. Universität Heidelberg

Daniel Garrido Norambuena (Former Master degree student 2014-2017)
Biochemist at Laboratorio Quimica Clínica Especializada.

Sergio Hernández Tapia (Former Ph.D. student, 2013-2017)
Post-doctoral fellow at University of Marseille

Jocelyn Neira (Former Ph.D. student 2013-2017)
Head of the Flow Cytometer Facility at UNAB

Cristian Doñas Cuadra (Former undergraduate student and Ph.D. student, 2012-2017)
Post-doctoral fellow at Karolinska Institutet, Sweden

Lorena Rubio Quiroz (Former Master degree student 2013-2016)

Paola Merino (Former post-doctoral fellow, 2015)
Post-doctoral fellow at Emory University

Yvo Flores León (Former Master degree student 2013-2015)
Research assistant at INIA

Carlos Rivera Alvarez (Former Master degree student 2013-2015)
Ph.D. student at Pontificia Universidad Católica de Chile/Massachusetts General Hospital, Harvard Medical School

Germán Púas Villega (Former undergraduate student, 2012-2014)
Master of Philosophy, Universidad Santiago de Chile

Macarena Fritz Kelly (Former Ph.D. student, 2009-2013)

César Díaz Célis (Former post-doctoral fellow, 2012)
Post-doctoral fellow at HHMI/University of California

Valentina Ugalde Tagle (Former Master degree student 2009-2011)
Research assistant at Fundacion Ciencia & Vida

SELECTED PUBLICATIONS

  • Alvarez F., Garrido D., Varas-Godoy M., Gutiérrez JL., Villanueva RA. and Loyola A. (2021) “The Histone Variant H3.3 Regulates the Transcription of the Hepatitis B Virus”. Annals of Hepatolgy. 21:100261. DOI: 10.1016/j.aohep.2020.09.005. | | ABSTRACT
  • Doñas C., Neira J., Osorio-Barrios F., Carrasco M., Prado C., Loyola A., Pacheco R. and Rosemblatt M. (2021) “The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells”. Scientific Reports. 11(1):1342. DOI: 10.1038/s41598-020-79122-3. | | ABSTRACT
  • Escobar T., *Loyola A. and Reinberg D. “Parental nucleosome segregation and the inheritance of cellular identity”. (2021) Nature Reviews Genetics. https://doi.org/10.1038/s41576-020-00312-w. *equal contribution | | ABSTRACT
  • Prieto, C.; Montecinos, J.; Jim, G.; Riquelme, C.; Garrido, D.; Hern, S.; Loyola, A.; Villanueva, R.A. “Phosphorylation of phylogenetically conserved amino acid residues confines HBx within different cell compartments of human hepatocarcinoma cells”. Molecules, 26, 1254. https://doi.org/10.3390/molecules26051254. | | ABSTRACT
  • Saavedra F., Gurard-Levin ZA., Rojas-Villalobos C., Vassias I., Quatrini R., Almouzni G., Loyola A. JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability. Epigenetics & Chromatin. 13:6. DOI: 10.1186/s13072-020-00331-1 (2020) | PDF | ABSTRACT
  • Flores-Rios R., Quatrini R., Loyola A. Endogenous and Foreign Nucleoid-Associated Proteins of Bacteria: occurrence, interactions and effects on Mobile Genetic Elements and host ́s biology. Computational and Structural Biotechnology Journal. 17: 746-756. DOI: https://doi.org/10.1016/j.csbj.2019.06.010 (2019) | PDF | ABSTRACT
  • Hernández S., Díaz A., Loyola A., Villanueva RA. Recombinant HCV NS3 and NS5b enzymes exhibit multiple posttranslational modifications for potential regulation. Virus Genes. 55 (2): 227-232. DOI: 10.1007/s11262-019-01638-2 (2019) | PDF | ABSTRACT
  • Saavedra F., Boyarchuk E., Alvarez F., Almouzni G., Loyola A. Metabolic deregulations affecting chromatin architecture: One-carbon metabolism and Krebs cycle impact histone methylation. In: The DNA, RNA, and Histone Methylomes, edited by S. Jurga and J. Barciszewski., vol 9. RNA TECHNOLOGIES, Springer Series (2019) | PDF | ABSTRACT
  • Saavedra F., Marty-Lombardi S., Loyola A. Characterization of Posttranslational Modifications on Histone Variants”. In: Histone Variants. Methods in Molecular Biology, edited by G. Orsi G and G. Almouzni, vol 1832. Humana Press, New York, NY. DOI: 10.1007/978-1-4939-8663-7_2 (2018) | PDF | ABSTRACT
  • Álvarez F., Loyola A. Histone variants: Structure, function and implication in diseases (Chapter 7). In: Gene Regulation, Epigenetics and Hormone Signaling, edited by Dr. S. Mandal. Publishing Editor: Gregor Cicchetti. Wiley-VCH in Weinheim, Germany. Pp: 209-226. DOI: 10.1002/9783527697274.ch7 (2017) | | ABSTRACT
  • Saavedra F., Rivera C., Rivas E., Merino P., Garrido D., Hernández S., Forné I., Vassias I., Gurard-Levin Z.A., Alfaro I.E., Imhof A., Almouzni G.A., Loyola A. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4. Nucleic Acids Res. 45 (20): 11700-11710. DOI: 10.1093/nar/gkx775 (2017) | | ABSTRACT
  • 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) | PDF | 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