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Chromatin supraorganization, chromosome anomalies and cell death under conditions of histone deacetylase inhibition in HeLa and 3T3 cells

Grant number: 09/11763-0
Support Opportunities:Scholarships in Brazil - Master
Start date: August 01, 2010
End date: February 29, 2012
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Maria Luiza Silveira Mello
Grantee:Marina Barreto Felisbino
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

In eukaryotic cells chromatin results from the organization of nucleoprotein complexes into nucleosomes and of these ones into a higher hierarchical organization. The functional dynamics of the chromatin is especially related to histone and DNA modifications and iRNA action. Acetylation, deacetylation, methylation and demethylation are forms of histone modifications. Deacetylases that mostly act on histones H3 and H4 are often associated with gene silencing and their inhibition is related to gene expression. How histone modifiers or their inhibition affect the levels of chromatin organization and supraorganization and cell physiology is currently under discussion. Considering that valproic acid (VPA) is a potent inhibitor of histone deacetylases, its effect on chromatin supraorganization, chromosome anomalies and cell death will be studied in two models, HeLa and 3T3 cells, using microspectrophotometry and ordinary microscopy. The results to be obtained after treatment of the cells with different VPA concentrations at various time exposures will be compared with data using trichostatin-A (TSA) as a positive control. For the case of the 3T3 cells, this study will be preceded by investigation of cell viability with MTT and Trypan Blue exclusion assays in VPA- and TSA-treated preparations. In the case of HeLa cells this information is already available. The activity of histone deacetylases and the acetylation levels of histones H3 and H4 after treatment with VPA will be considered for the interpretation of chromatin supraorganization patterns, chromosome anomalies and cell death. (AU)

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Scientific publications
(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)
FELISBINO, MARINA BARRETO; VICCARI GATTI, MARIA SILVIA; MELLO, MARIA LUIZA S.. Changes in Chromatin Structure in NIH 3T3 Cells Induced by Valproic Acid and Trichostatin A. Journal of Cellular Biochemistry, v. 115, n. 11, p. 1937-1947, . (09/11763-0, 10/50015-6)
FELISBINO, MARINA BARRETO; TAMASHIRO, WIRLA M. S. C.; MELLO, MARIA LUIZA S.. Chromatin Remodeling, Cell Proliferation and Cell Death in Valproic Acid-Treated HeLa Cells. PLoS One, v. 6, n. 12, . (09/11763-0, 10/50015-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FELISBINO, Marina Barreto. Chromatin remodeling, chromosome abnormalities and cell death under histone deacetylase inhibition in HeLa and 3T3 cells. 2012. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.