Relationship between Core Histone Acetylation and Histone H1⁰ Gene Activity

Abstract

In this study we show a striking correlation between histone H1(0) gene expression and histone acetylation. Trichostatin A, a highly specific inhibitor of histone deacetylase, efficiently induces H1(0) gene expression. Moreover, using a cell line sensitive to trichostatin A (FM3A) and a derived cell line selected for its resistance to this inhibitor (TR303), it is shown that the level of H1(0) gene expression is related to the extent of chromatin acetylation. After showing the S-phase-dependent activation of H1(0) gene expression, we demonstrate that hyperacetylation has a dominant effect on H1(0) gene expression, since it enhances the expression of the gene independent of the position of cells in the cell cycle. This response to deacetylase inhibitors is specific to H1(0), since it is not shared by other cell-cycle-dependent histone genes (H1 and H4). Finally, by transfection of trichostatin-A-resistant and trichostatin-A-sensitive cells with a plasmid containing a H1(0) promoter, we show that the exogenous H1(0) promoter is also highly sensitive to trichostatin A treatment and that activation of transcription follows exactly the same pattern as activation of the endogenous gene. These data show that histone acetylation may be used to modulate H1(0) gene activity and offers insight into a possible mechanism in which the developmentally regulated chromatin acetylation acts to potentiate H1(0) gene expression.

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

“…However, acetylation of a single lysine has been shown to alter binding affinity of proteins; for example, binding of highmobility-group 1 (HMG1) protein to DNA (Ugrinova et al, 2001) and binding of nuclear steroid hormone receptors to the ACTR coactivator (Chen et al, 1999). Analogously, monoacetylation of histone H4 is sufficient to alter recognition by transcriptional machinery (Girardot et al, 1994). Although acetylation exerts a milder effect on protein activity than phosphorylation (Polevoda and Sherman, 2002), modification of many subunits along a macromolecular structure such as a MT may propagate and, thus, enhance a modest effect.…”

Identification of a New Family of Higher Eukaryotic Histone Deacetylases

“…FM3A and TR303 cell lines were treated with different concentrations of trichostatin A for 6 h. Cells were lysed, and histones were purified and analyzed on a Triton/acid/urea gel as described previously (20). The appearance of hyperacetylated H4 was also monitored using antibody raised against hyperacetylated histone H4 (Upstate Biotechnology Inc.) followed by cytofluorimetric measurement of immunofluorescence according to the published protocol (21).…”

Identification of Mouse Histone Deacetylase 1 as a Growth Factor-Inducible Gene

“…Another important step toward the understanding of the role of histone acetylation was the identification of specific inhibitors of histone deacetylases (12; for a review, see reference 77). Trichostatin A, a fungistatic antibiotic, has been shown to induce differentiation in erythroleukemia cells (78), to block the development of Xenopus and starfish embryos (2), to induce the expression of different genes (5,20,25,43), and to arrest normal fibroblasts in the G 1 or G 2 phase of the cell cycle (76). Furthermore, trichostatin A and trapoxin, another specific inhibitor of histone deacetylases, also have the potential to revert the phenotype of oncogene-transformed fibroblasts (17,62,75).…”