The Effects of Histone Acetylation on Estrogen Responsiveness in MCF-7 Cells

Ruh, Mary F.; Tian, Shengping; Cox, Linda K.; Ruh, Thomas S.

doi:10.1385/endo:11:2:157

Cited by 14 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the situation in which AF-1 is important for transactivation, ERa is a better activator than ERb, whereas both receptors display equivalent potencies when only AF-2 is required. A supra-additive action of HDI and nuclear receptor ligands has been reported for ERa (Ruh et al, 1999) and also for PR (Liu et al, 1999), retinoid receptors (Minucci et al, 1997), PPARg (Fajas et al, 2003), AR (Shang et al, 2002) and TR (Stanley and Samuels, 1984), suggesting that this is a general phenomenon.…”

Section: Discussionmentioning

confidence: 89%

ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors

et al. 2005

View full text Add to dashboard Cite

The proliferative action of ERa largely accounts for the carcinogenic activity of estrogens. By contrast, recent data show that ERb displays tumor-suppressor properties, thus supporting the interest to identify compounds that could increase its activity. Here, we show that histone deacetylase inhibitors (HDI) upregulated ERb protein levels, whereas it decreased ERa expression. Part of this regulation took place at the mRNA level through a mechanism independent of de novo protein synthesis. In addition, we found that, in various cancer cells, the treatment with different HDI enhanced the liganddependent activity of ERb more strongly than that of ERa. On the other hand, in MDA-MB231 and HeLa cells, the expression of ERs modified the transcriptional response to HDI. The use of deletion mutants of both receptors demonstrated that AF1 domain of the receptors was required. Finally, we show that ERb expression led to a dramatic increased in the antiproliferative activity of HDI, which correlated with a modification of the transcription of genes involved in cell cycle control by HDI. Altogether, these data demonstrate that the interference of ERb and HDAC on the control of transcription and cell proliferation constitute a promising approach for cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 89%

ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors

et al. 2005

View full text Add to dashboard Cite

show abstract

“…As with H3, the acetylation of lysine residues located on the N terminus of histone H4 are important for transcriptional processes (15,64). Lysine 5 acetylation is associated with the derepression of some genes (65), and lysine 8 acetylation was shown to dramatically increase at the interferon-␤ promoter following viral infection (15).…”

Section: Discussionmentioning

confidence: 99%

The Expression of Endothelial Nitric-oxide Synthase Is Controlled by a Cell-specific Histone Code

Fish¹,

Matouk

Rachlis

et al. 2005

Journal of Biological Chemistry

209

189

View full text Add to dashboard Cite

Expression of endothelial nitric-oxide synthase (eNOS) mRNA is highly restricted to the endothelial cell layer of medium to large sized arterial blood vessels. Here we assessed the chromatin environment of the eNOS gene in expressing and nonexpressing cell types. Within endothelial cells, but not a variety of nonendothelial cells, the nucleosomes that encompassed the eNOS core promoter and proximal downstream coding regions were highly enriched in acetylated histones H3 and H4 and methylated lysine 4 of histone H3. This differentially modified chromatin domain was selectively associated with functionally competent RNA polymerase II complexes. Endothelial cells were particularly enriched in acetylated histone H3 lysine 9, histone H4 lysine 12, and di-and tri-methylated lysine 4 of histone H3 at the core promoter. Histone modifications at this region, which we have previously demonstrated to exhibit cell-specific DNA methylation, were functionally relevant to eNOS expression. Inhibition of histone deacetylase activity by trichostatin A increased acetylation of histones H3 and H4 at the eNOS proximal promoter in nonexpressing cell types and led to increased steadystate eNOS mRNA transcript levels. H3 lysine 4 methylation was also essential for eNOS expression, since treatment of endothelial cells with methylthioadenosine, a known lysine 4 methylation inhibitor, decreased eNOS RNA levels, H3 lysine 4 methylation, and RNA polymerase II loading at the eNOS proximal promoter. Importantly, methylthioadenosine also prevented the trichostatin A-mediated increase in eNOS mRNA transcript levels in nonendothelial cells. Taken together, these findings provide strong evidence that the endothelial cell-specific expression of eNOS is controlled by cell-specific histone modifications.Endothelial nitric-oxide synthase (eNOS, 1 NOS3) is constitutively expressed in vascular endothelial cells, especially the endothelial layer of medium to large sized arterial blood vessels, where it is known to play a key role in vascular wall homeostasis and regulation of vasomotor tone. Studying the mechanisms regulating the constitutive transcription of eNOS in endothelial cells is essential to understand how these mechanisms may be perturbed in diseases characterized by a decrease in eNOS mRNA in the vascular endothelium. For example, constitutive expression of eNOS is compromised in the endothelial cells overlying advanced human atherosclerotic plaques (1-3).In general, the basis for endothelium-specific gene expression is not known. Whereas models involving DNA-binding transcription factors (e.g. AP-1, Ets family members, GATA-2, octamer proteins, or Sp1) (4 -7) have been invoked to explain the transcriptional control of a variety of endothelial genes, these models cannot fully account for the exquisite specificity of these endothelium-specific promoters, given that these transfactors are ubiquitously expressed. This can be contrasted with the control of muscle-specific or adipocyte-specific genes, which are controlled by "master regulators," i...

show abstract

“…Although sodium butyrate inhibited glucocorticoid induction of the tyrosine aminotransferase gene in rat HTC cells (Plesko et al, 1983), it enhanced glucocorticoid induction of alkaline phosphatase in HeLa S3 cells (Littlefield and Cidlowski, 1984). Finally, trichostatin A induced estrogen-dependent transcription in MCF-7 cells (Ruh et al, 1999) and in stably transfected HepG2 cells (Mao and Shapiro, 2000).…”

mentioning

confidence: 99%

Opposite Effects of Histone Deacetylase Inhibitors on Glucocorticoid and Estrogen Signaling in Human Endometrial Ishikawa Cells

Rocha

Sánchez²,

Deschênes³

et al. 2005

Mol Pharmacol

View full text Add to dashboard Cite

Histone deacetylase inhibitors (HDACi), which have emerged as a new class of anticancer agents, act by modulating expression of genes controlling apoptosis or cell proliferation. Here, we compared the effect of HDACi on transcriptional activation by estrogen or glucocorticoid receptors (ER and GR, respectively), two members of the steroid receptor family with cell growth regulatory properties. Like other transcription factors, steroid receptors modulate histone acetylation on target promoters. Using episomal reporter vectors containing minimal promoters to avoid promoter-specific effects, we observed that long-term (24-h) incubation with HDACi strongly stimulated GR-dependent but markedly repressed ER-dependent signaling in ER+/GR+ human endometrial carcinoma Ishikawa cells. These effects were reproduced on endogenous target genes and required incubation periods with HDACi substantially longer than necessary to increase global histone acetylation. Repression of estrogen signaling was due to direct inhibition of transcription from multiple ERalpha promoters and correlated with decreased histone acetylation of these promoters. In contrast, the strong HDACi stimulation of GR-dependent gene regulation was not accounted for by increased GR expression, but it was mimicked by overexpression of the histone acetyltransferase complex component transcriptional intermediary factor 2. Together, our results demonstrate striking and opposite effects of HDACi on ER and GR signaling that involve regulatory events independent of histone hyperacetylation on receptor target promoters.

show abstract

The Effects of Histone Acetylation on Estrogen Responsiveness in MCF-7 Cells

Cited by 14 publications

References 46 publications

ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors

ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors

The Expression of Endothelial Nitric-oxide Synthase Is Controlled by a Cell-specific Histone Code

Opposite Effects of Histone Deacetylase Inhibitors on Glucocorticoid and Estrogen Signaling in Human Endometrial Ishikawa Cells

Contact Info

Product

Resources

About