API

Event: 1503

Key Event Title

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Histone acetylation, increase

Short name

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Histone acetylation, increase

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Cell term
cell


Organ term

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Organ term
organ


Key Event Components

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Process Object Action
regulation of protein modification process histone increased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Taxonomic Applicability

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Life Stages

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Life stage Evidence
Not Otherwise Specified Moderate

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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Gene transcription is regulated with the balance between acetylation and deacetylation. The acetylation and deacetylation are modulated on the NH3+ groups of lysine amino acid residues in histones. DNA in acetylated histones is more accessible for transcription factors, leading to increase in gene expression. HDAC inhibition promotes the hyperacetylation by inhibiting deacetylation of histones with classes of H2A, H2B, H3 and H4 in nucleosomes. [Wade, 2008].


How It Is Measured or Detected

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Histone acetylation is measured by the immunological detection of histone acetylation with anti-acetylated histone antibodies [Richon, 2004]. Histone acetylation on chromatin can be measured using labeling method with sodium [3H] acetate [Gunjan, 2001].


Domain of Applicability

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The histone acetylation increase by HDIs is well conserved between species from lower organism to mammals.

・MAA, a HDAC inhibitor, induces acetylation of histones H3 and H4 in Sprague-Dawley (Rattus norvegicus) [Wade, 2008].

・It is also reported that MAA promotes acetylation of H4 in HeLa cells (Homo sapiens) and spleens from C57BL/6 mice (Mus musculus) treated with MAA [Jansen, 2014].

・VPA, a HDAC inhibitor, induces hyperacetylation of histone H4 in protein extract of mouse embryos (Mus musculus) exposed in utero for 1h to VPA [Di Renzo, 2007a].

・Apicidin, MS-275 and sodium butyrate, HDAC inhibitors, induce hyperacetylation of histone H4 in homogenates from mouse embryos (Mus musculus) after the treatments [Di Renzo, 2007b].

・MAA acetylates histones H3K9 and H4K12 in limbs of CD1 mice (Mus musculus) [Dayan, 2014].


References

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Wade MG et al. (2008) Methoxyacetic acid-induced spermatocyte death is associated with histone hyperacetylation in rats. Biol Reprod 78:822-831

Richon VM et al. (2004) Histone deacetylase inhibitors: assays to assess effectiveness in vitro and in vivo. Methods Enzymol 376:199-205

Gunjan A et al. (2001) Core histone acetylation is regulated by linker histone stoichiometry in vivo. J Biol Chem 276:3635-3640

Jansen MS et al. (2014) Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition Proc Natl Acad Sci USA 101:7199-7204

Di Renzo F et al. (2007a) Boric acid inhibits embryonic histone deacetylases: A suggested mechanism to explain boric acid-related teratogenicity. Toxicol and Appl Pharmacol 220:178-185

Di Renzo F et al. (2007b) Relationship between embryonic histonic hyperacetylation and axial skeletal defects in mouse exposed to the three HDAC inhibitors apicidin, MS-275, and sodium butyrate. Toxicol Sci 98:582-588

Dayan C and Hales BF. (2014) Effects of ethylene glycol monomethyl ether and its metabolite, 2-methoxyacetic acid, on organogenesis stage mouse limbs in vitro. Birth Defects Res (Part B) 101:254-261