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Action of valproic acid on chromatin structure and function

Grant number: 15/10356-2
Support type:Research Projects - Thematic Grants
Duration: May 01, 2017 - April 30, 2022
Field of knowledge:Biological Sciences - Genetics - Animal Genetics
Principal Investigator:Maria Luiza Silveira Mello
Grantee:Maria Luiza Silveira Mello
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Co-Principal Investigators:Benedicto de Campos Vidal
Assoc. researchers:Luciana Bolsoni Lourenço ; Maria Silvia Viccari Gatti ; Wirla Maria da Silva Cunha Tamashiro
Associated scholarship(s):19/20833-3 - Epigenetic markers responsive to sodium valproate in the heterocrhomatin of Triatoma infestans (Klug), BP.PD
18/07888-0 - Effects of the valproic acid (VPA) on the chromatin of Malpighian tubules of Triatoma infestans under in vitro conditions, BP.IC

Abstract

The action of Valproic Acid (VPA), a histone deacetylase inhibitor, has been investigated in several cell models under various experimental conditions. VPA has also been considered for clinical applications because of its modulating activity on gene expression. VPA affects different types of epigenetic marks through mechanisms that vary, depending on cell types and their physiological/pathological conditions, and which are not fully understood. Described VPA action mechanisms involve interference on levels of histone acetylation with predominance of induction of H3K9 and H4K8 acetylation, DNA demethylation and histone methylation and/or demethylation. Present proposal aims to bring contribution on how different metabolic pathways of the VPA action express at chromatin structural and functional levels in some cell types. The issues addressed are the following: 1. What changes are promoted by VPA at the H3K9/14 acetylation levels that could reflect on differential gene expression in certain genetic pathways of interest in a liver cell model under hyperglycemic microenvironment? 2. What is the level of DNA methylation that is affected by VPA in cells where this drug inhibits histone deacetylases and promotes H3K9 and H4K8 acetylation and chromatin remodeling, and how this phenomenon works (passive or active via)? 3. By what mechanism VPA allows unraveling of heterochromatic bodies without involvement of H3K9 and H4K8 acetylation? The methodology will involve ChIP-seq and RNA-seq assays, immunoassays, bioinformatics, image analysis, flow cytometry, confocal microscopy, laser microsurgery and infrared microspectroscopy. (AU)

Articles published in other media outlets (22 total):
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UOL: Remédio para convulsão modifica o DNA e interage com proteínas, diz estudo (21/Dec/2020)
Consenso Salud (Argentina): El ácido valproico puede modificar el ADN e interactuar con proteínas de los cromosomas (29/Dec/2020)
ICTQ - Instituto de Ciência, Tecnologia e Qualidade: Droga para convulsão pode modificar DNA, diz estudo (23/Dec/2020)
Revista Amazônia: Droga anticonvulsiva pode modificar o DNA e interagir com proteínas dos cromossomos (21/Dec/2020)
LabNetwork: Droga anticonvulsiva pode modificar o DNA e interagir com proteínas dos cromossomos (21/Dec/2020)
Revista Analytica online: Droga anticonvulsiva pode modificar o DNA e interagir com proteínas dos cromossomos (21/Dec/2020)
Saense: Droga anticonvulsiva pode modificar o DNA e interagir com proteínas dos cromossomos (21/Dec/2020)
Portal da Enfermagem: Droga anticonvulsiva pode modificar o DNA e interagir com proteínas dos cromossomos (21/Dec/2020)
Programa InfoSalud (Argentina): Una droga anticonvulsiva puede modificar el ADN e interactuar con proteínas de los cromosomas (21/Dec/2020)
News Medical (Austrália): Valproic acid can interact with DNA conformation and regulate gene expression (29/Sep/2020)
Mindzilla (Reino Unido): Anti-Convulsant Drug can Modify DNA Conformation and Interact with Chromosome Proteins (29/Sep/2020)
Sound Health and Lasting Wealth (Nigéria): Valproic acid can interact with DNA conformation and regulate gene expression (29/Sep/2020)
Nestia (Singapura): Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (29/Sep/2020)
Knowledia (França): Valproic acid can interact with DNA conformation and regulate gene expression (29/Sep/2020)
QNewsHub (Índia): Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (29/Sep/2020)
Eminetra Today (EUA): Valproic acid can interact with DNA conformation and regulate gene expression (29/Sep/2020)
Eurekalert (EUA): Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (28/Sep/2020)
Phys.Org (Reino Unido): Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (28/Sep/2020)
Science Codex: Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (28/Sep/2020)
Scienmag Science Magazine (Reino Unido): Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (28/Sep/2020)
7thSpace: Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (28/Sep/2020)
Burada Biliyorum (Turquia): Anti-convulsant drug can modify DNA conformation and interact with chromosome proteins (28/Sep/2020)

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VIDAL, BENEDICTO DE CAMPOS; MELLO, MARIA LUIZA S. Sodium valproate (VPA) interactions with DNA and histones. International Journal of Biological Macromolecules, v. 163, p. 219-231, NOV 15 2020. Web of Science Citations: 0.
IMPERADOR, CARLOS HENRIQUE L.; BARDELLA, VANESSA B.; DOS ANJOS, ELI HEBER M.; RODRIGUES, VERA L. C. C.; CABRAL-DE-MELLO, DIOGO C.; MELLO, MARIA LUIZA S. Spatial Distribution of Heterochromatin Bodies in the Nuclei ofTriatoma infestans(Klug). Microscopy and Microanalysis, v. 26, n. 3, p. 567-574, JUN 2020. Web of Science Citations: 0.
ROCHA, MARINA AMORIM; BREDA VERONEZI, GIOVANA MARIA; FELISBINO, MARINA BARRETO; VICCARI GATTI, MARIA SILVIA; TAMASHIRO, WIRLA M. S. C.; SILVEIRA MELLO, MARIA LUIZA. Sodium valproate and 5-aza-2 `-deoxycytidine differentially modulate DNA demethylation in G1 phase-arrested and proliferative HeLa cells. SCIENTIFIC REPORTS, v. 9, DEC 3 2019. Web of Science Citations: 0.
VIDAL, BENEDICTO DE CAMPOS; MELLO, MARIA LUIZA S. Toluidine blue staining for cell and tissue biology applications. ACTA HISTOCHEMICA, v. 121, n. 2, p. 101-112, 2019. Web of Science Citations: 2.
ALVARENGA, ELENICE M.; IMPERADOR, CARLOS H. L.; BARDELLA, VANESSA B.; RODRIGUES, VERA L. C. C.; MONDIN, MATEUS; CABRAL-DE-MELLO, DIOGO C.; MORAES, ALBERTO S.; MELLO, MARIA LUIZA S. Histone acetylation and methylation marks in chromatin of Panstrongylus megistus (Hemiptera, Reduviidae). ACTA HISTOCHEMICA, v. 120, n. 6, p. 572-577, 2018. Web of Science Citations: 0.
VIDAL, BENEDICTO DE CAMPOS; MELLO, MARIA LUIZA S. Chiral supramolecular order revealed during the formation of calf thymus and phage DNA crystals. Micron, v. 102, p. 44-50, NOV 2017. Web of Science Citations: 1.
MELLO, MARIA LUIZA S.; VIDAL, BENEDICTO DE CAMPOS. The Feulgen reaction: A brief review and new perspectives. ACTA HISTOCHEMICA, v. 119, n. 6, p. 603-609, 2017. Web of Science Citations: 5.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.