Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic mechanisms: dynamic chromosomal interactions

Abstract

To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH₂), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications.

Keywords:

• Graphene oxide
• cox2
• chromatin interactions
• surface modification
• apoptosis

View correction statement:

Correction to: Sun et al. Graphene oxide regulates cox2 in human embryonic kidney 293 T cells via epigenetic mechanisms: dynamic chromosomal interactions

Acknowledgements

We thank Dr He Zhang for great assistance with 3C analysis. We thank all the laboratory members for their great assistance with experiments and reagents.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This study was supported by the National Basic Research 973 Program (2014CB932002), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB14030502), and the National Natural Science Foundation of China grants (81273004 and 31470829).