Changes in Chromatin Structure in NIH 3T3 Cells Induced by Valproic Acid and Trichostatin A

Author(s)

Felisbino, Marina Barreto ^[1] ; Viccari Gatti, Maria Silvia ^[2] ; Mello, Maria Luiza S. ^[1]

Affiliation

^[1] Univ Campinas Unicamp, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, BR-13083862 Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Cellular Biochemistry; v. 115, n. 11, p. 1937-1947, NOV 2014.
• Web of Science Citations: 15

Abstract

Valproic acid (VPA) and trichostatin A (TSA) are known histone deacetylase inhibitors (HDACIs) with epigenetic activity that affect chromatin supra-organization, nuclear architecture, and cellular proliferation, particularly in tumor cells. In this study, chromatin remodeling with effects extending to heterochromatic areas was investigated by image analysis in non-transformed NIH 3T3 cells treated for different periods with different doses of VPA and TSA under conditions that indicated no loss of cell viability. Image analysis revealed chromatin decondensation that affected not only euchromatin but also heterochromatin, concomitant with a decreased activity of histone deacetylases and a general increase in histone H3 acetylation. Heterochromatin protein 1- (HP1-), identified immunocytochemically, was depleted from the pericentromeric heterochromatin following exposure to both HDACIs. Drastic changes affecting cell proliferation and micronucleation but not alteration in CCND2 expression and in ratios of Bcl-2/Bax expression and cell death occurred following a 48-h exposure of the NIH 3T3 cells particularly in response to higher doses of VPA. Our results demonstrated that even low doses of VPA (0.05mM) and TSA (10ng/ml) treatments for 1h can affect chromatin structure, including that of the heterochromatin areas, in non-transformed cells. HP1- depletion, probably related to histone demethylation at H3K9me3, in addition to the effect of VPA and TSA on histone H3 acetylation, is induced on NIH 3T3 cells. Despite these facts, alterations in cell proliferation and micronucleation, possibly depending on mitotic spindle defects, require a longer exposure to higher doses of VPA and TSA. J. Cell. Biochem. 115: 1937-1947, 2014. (c) 2014 Wiley Periodicals, Inc. (AU)

• FAPESP's process: 09/11763-0 - Chromatin supraorganization, chromosome anomalies and cell death under conditions of histone deacetylase inhibition in HeLa and 3T3 cells
• Grantee: Marina Barreto Felisbino
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 10/50015-6 - Chromatin structure and organization with aging and diabetes compared to induced changes in epigenetic markers
• Grantee: Maria Luiza Silveira Mello
• Support type: Research Projects - Thematic Grants