Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle

Autores
Balestrasse, Malena; Massimino Stepñicka, Milena; Alonso, Guillermo Daniel; Ocampo, Josefina
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Trypanosome cruzi, the ethiologic agent of Chagas Disease, affects a large number of the population in Latin America. It has a complex life cycle alternating between a mammalian host and the vector insect, Triatoma infestans. This cycle consists of three well-defined stages: amastigotes, epimastigotes and trypomastigotes. When the parasite faces different environments, it requires changes in gene expression in order to survive. Hence, gene expression regulation modulated by chromatin organization might be a key aspect to understand adaptation. Despite Trypanosomes gene expression is mainly regulated post transcriptionally, there are evidences that chromatin influence gene expression regulation. Recent studies have shown that homologues DOT1 methyltransferases, called DOT1a and DOT1b, are involved in the methylation of lysine 76 of histone H3 in T. cruzi. In T. brucei, DOT1a mediates H3K76 mono and di-methylation, whereas DOT1b also catalyzes H3K76 tri-methylation. However, these two enzymes remain poorly characterized.In this project, we intend to characterize the enzymatic activity and study the relevance of TcDOT1a and TcDOT1b during cell cycle and the metacytogenesis process. Therefore, to evaluate the catalytic activity using, we have successfully cloned and transformed a null DOT1 yeast strain with TcDOT1a. We are currently evaluating heterologous complementation. Simultaneously, we are working on TcDOT1b. Additionally, to analyze the isoforms subcelular location and their effects on cell cycle progression and differentiation, we have cloned the TcDOT1 isoforms in a pRibotex vector with an N-terminal HA-tag and transfected CL-Brener strain. Unfortunately, it resulted toxic for the cell. We are currently switching to use an inducible vector. Overall, our data will be useful to further understand the role of the DOT1 isoforms and the differential methylation of H3K76 in T. cruzi. In the long term, our findings might unravel new targets search for antiparasitic drugs.
Fil: Balestrasse, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Massimino Stepñicka, Milena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ocampo, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Reunión Anual de Sociedades de Biociencias 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
CHROMATIN
TRYPANOSOMES
DOT1
EPIGENETICS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/201691
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/201691
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycleBalestrasse, MalenaMassimino Stepñicka, MilenaAlonso, Guillermo DanielOcampo, JosefinaCHROMATINTRYPANOSOMESDOT1EPIGENETICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosome cruzi, the ethiologic agent of Chagas Disease, affects a large number of the population in Latin America. It has a complex life cycle alternating between a mammalian host and the vector insect, Triatoma infestans. This cycle consists of three well-defined stages: amastigotes, epimastigotes and trypomastigotes. When the parasite faces different environments, it requires changes in gene expression in order to survive. Hence, gene expression regulation modulated by chromatin organization might be a key aspect to understand adaptation. Despite Trypanosomes gene expression is mainly regulated post transcriptionally, there are evidences that chromatin influence gene expression regulation. Recent studies have shown that homologues DOT1 methyltransferases, called DOT1a and DOT1b, are involved in the methylation of lysine 76 of histone H3 in T. cruzi. In T. brucei, DOT1a mediates H3K76 mono and di-methylation, whereas DOT1b also catalyzes H3K76 tri-methylation. However, these two enzymes remain poorly characterized.In this project, we intend to characterize the enzymatic activity and study the relevance of TcDOT1a and TcDOT1b during cell cycle and the metacytogenesis process. Therefore, to evaluate the catalytic activity using, we have successfully cloned and transformed a null DOT1 yeast strain with TcDOT1a. We are currently evaluating heterologous complementation. Simultaneously, we are working on TcDOT1b. Additionally, to analyze the isoforms subcelular location and their effects on cell cycle progression and differentiation, we have cloned the TcDOT1 isoforms in a pRibotex vector with an N-terminal HA-tag and transfected CL-Brener strain. Unfortunately, it resulted toxic for the cell. We are currently switching to use an inducible vector. Overall, our data will be useful to further understand the role of the DOT1 isoforms and the differential methylation of H3K76 in T. cruzi. In the long term, our findings might unravel new targets search for antiparasitic drugs.Fil: Balestrasse, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Massimino Stepñicka, Milena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ocampo, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaReunión Anual de Sociedades de Biociencias 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMedicina (Buenos Aires)Costas, Monica AlejandraMarino, Gabriela InésAzurmendi, Pablo Javier2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201691Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle; Reunión Anual de Sociedades de Biociencias 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 124-1250025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:45:51Zoai:ri.conicet.gov.ar:11336/201691instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:45:52.258CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
title Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
spellingShingle Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
Balestrasse, Malena
CHROMATIN
TRYPANOSOMES
DOT1
EPIGENETICS
title_short Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
title_full Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
title_fullStr Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
title_full_unstemmed Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
title_sort Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle
dc.creator.none.fl_str_mv Balestrasse, Malena
Massimino Stepñicka, Milena
Alonso, Guillermo Daniel
Ocampo, Josefina
author Balestrasse, Malena
author_facet Balestrasse, Malena
Massimino Stepñicka, Milena
Alonso, Guillermo Daniel
Ocampo, Josefina
author_role author
author2 Massimino Stepñicka, Milena
Alonso, Guillermo Daniel
Ocampo, Josefina
author2_role author
author
author
dc.contributor.none.fl_str_mv Costas, Monica Alejandra
Marino, Gabriela Inés
Azurmendi, Pablo Javier
dc.subject.none.fl_str_mv CHROMATIN
TRYPANOSOMES
DOT1
EPIGENETICS
topic CHROMATIN
TRYPANOSOMES
DOT1
EPIGENETICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosome cruzi, the ethiologic agent of Chagas Disease, affects a large number of the population in Latin America. It has a complex life cycle alternating between a mammalian host and the vector insect, Triatoma infestans. This cycle consists of three well-defined stages: amastigotes, epimastigotes and trypomastigotes. When the parasite faces different environments, it requires changes in gene expression in order to survive. Hence, gene expression regulation modulated by chromatin organization might be a key aspect to understand adaptation. Despite Trypanosomes gene expression is mainly regulated post transcriptionally, there are evidences that chromatin influence gene expression regulation. Recent studies have shown that homologues DOT1 methyltransferases, called DOT1a and DOT1b, are involved in the methylation of lysine 76 of histone H3 in T. cruzi. In T. brucei, DOT1a mediates H3K76 mono and di-methylation, whereas DOT1b also catalyzes H3K76 tri-methylation. However, these two enzymes remain poorly characterized.In this project, we intend to characterize the enzymatic activity and study the relevance of TcDOT1a and TcDOT1b during cell cycle and the metacytogenesis process. Therefore, to evaluate the catalytic activity using, we have successfully cloned and transformed a null DOT1 yeast strain with TcDOT1a. We are currently evaluating heterologous complementation. Simultaneously, we are working on TcDOT1b. Additionally, to analyze the isoforms subcelular location and their effects on cell cycle progression and differentiation, we have cloned the TcDOT1 isoforms in a pRibotex vector with an N-terminal HA-tag and transfected CL-Brener strain. Unfortunately, it resulted toxic for the cell. We are currently switching to use an inducible vector. Overall, our data will be useful to further understand the role of the DOT1 isoforms and the differential methylation of H3K76 in T. cruzi. In the long term, our findings might unravel new targets search for antiparasitic drugs.
Fil: Balestrasse, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Massimino Stepñicka, Milena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ocampo, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Reunión Anual de Sociedades de Biociencias 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Trypanosome cruzi, the ethiologic agent of Chagas Disease, affects a large number of the population in Latin America. It has a complex life cycle alternating between a mammalian host and the vector insect, Triatoma infestans. This cycle consists of three well-defined stages: amastigotes, epimastigotes and trypomastigotes. When the parasite faces different environments, it requires changes in gene expression in order to survive. Hence, gene expression regulation modulated by chromatin organization might be a key aspect to understand adaptation. Despite Trypanosomes gene expression is mainly regulated post transcriptionally, there are evidences that chromatin influence gene expression regulation. Recent studies have shown that homologues DOT1 methyltransferases, called DOT1a and DOT1b, are involved in the methylation of lysine 76 of histone H3 in T. cruzi. In T. brucei, DOT1a mediates H3K76 mono and di-methylation, whereas DOT1b also catalyzes H3K76 tri-methylation. However, these two enzymes remain poorly characterized.In this project, we intend to characterize the enzymatic activity and study the relevance of TcDOT1a and TcDOT1b during cell cycle and the metacytogenesis process. Therefore, to evaluate the catalytic activity using, we have successfully cloned and transformed a null DOT1 yeast strain with TcDOT1a. We are currently evaluating heterologous complementation. Simultaneously, we are working on TcDOT1b. Additionally, to analyze the isoforms subcelular location and their effects on cell cycle progression and differentiation, we have cloned the TcDOT1 isoforms in a pRibotex vector with an N-terminal HA-tag and transfected CL-Brener strain. Unfortunately, it resulted toxic for the cell. We are currently switching to use an inducible vector. Overall, our data will be useful to further understand the role of the DOT1 isoforms and the differential methylation of H3K76 in T. cruzi. In the long term, our findings might unravel new targets search for antiparasitic drugs.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/201691
Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle; Reunión Anual de Sociedades de Biociencias 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 124-125
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201691
identifier_str_mv Characterization of the TcDot1A and TcDot1B isoforms: Implication of H3K76 differential methylation during Trypanosoma cruzi life cycle; Reunión Anual de Sociedades de Biociencias 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 124-125
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Medicina (Buenos Aires)
publisher.none.fl_str_mv Medicina (Buenos Aires)
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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