Ultraviolet Radiation‐induced Transcription is Associated with Gene‐specific Histone Acetylation

Abstract

UVR is an important environmental carcinogen and a powerful modulator of the cutaneous immune system. Exposure to UVR activates many signaling pathways leading to changes in the expression of several hundred genes. While the covalent modification of histones has been shown to play a central role in regulating gene expression, the impact of UVR on histone modifications and the contribution of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the UVR-induced transcriptional response have not been completely characterized. In this report, we have examined the impact of UVR on histone H3 K9/14 acetylation. The potential role of UVR-induced histone acetylation in the UVR transcriptional response was also explored using the HAT inhibitor curcumin and HDAC inhibitor trichostatin A (TSA). We found that UVR caused an increase in histone H3 acetylation within the promoter regions of ATF3, COX2, IL-8, MKP1 and MnSOD. In most of the regions examined, histone H3 acetylation peaked 24 h after UVR and then returned to baseline levels by 72 h. The induction of ATF3, COX2 and MKP1 was blocked in the presence of curcumin at doses that decrease in vivo histone H3 acetylation but not at lower doses that do not affect acetylation levels. We also provide evidence that for ATF3, a transcriptional superinduction occurs after repeat exposures to UVR that can be recapitulated when the second UVR exposure is replaced with TSA treatment. Thus, UVR can alter histone acetylation within human keratinocytes and these changes may contribute to the UVR-transcriptional response.

Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases

“…Interestingly, HDAC1 was found to bind to the Fas promoter in T cells (56), which suggests that different HDACs may play role in regulation of Fas in different cells or tissues. pollack et al observed an increase at the level of histone H3 acetylation following UVR exposure at several gene promoters, such as ATF3, COX2 and IL-8, but no increase at the promoter region of the MHC class II gene in HaCaT cells (54). Consistent with their data, which suggest gene promoter specificity following exposure to radiation, we did not observe changes at the GApDH promoter acetylation following IR in our current study (Fig.…”

“…Several studies have reported that radiation can alter histone modifications (53)(54)(55), however, the direct effect of radiation on histone acetylation and HDACs remains unclear. It has been reported that DR4 expression was downregulated in medulloblastoma tumor samples and increased histone H3 and H4 acetylation at the DR4 promoter sensitized medulloblastoma cell lines to TRAIL-induced apoptosis (47).…”

Less Is More: Ebola Virus Surface Glycoprotein Expression Levels Regulate Virus Production and Infectivity

“…RNA isolation and reverse transcription (RT) were performed as previously described (42). Quantitative real-time PCR was performed by using a CFX96 thermal cycler (BioRad, Hercules, CA) and measuring the SYBR green incorporation into double-stranded amplicons.…”

Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes

“…Immunohistochemistry (IHC) was carried out at the Winship Cancer Institute Pathology Core Laboratory as previously reported (10). All skin biopsy sections were stained for either MHCI or MHCII at the same time and under the same conditions.…”

“…RNA isolation and reverse transcription were carried out as previously described (10,11). Quantitative real-time PCR was carried out using a CFX96 thermal cycler and measuring SYBR green incorporation into double-stranded amplicons.…”