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PLK-1 Interacting Checkpoint Helicase, PICH, Mediates Cellular Oxidative Stress Response

Overview
Journal Epigenomes
Date 2022 Oct 24
PMID 36278682
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Abstract

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation, often implemented by chromatin remodeling proteins. The study presented here shows that the expression of PICH, a Rad54-like helicase belonging to the ATP-dependent chromatin remodeling protein family, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response in both the absence and presence of oxidative stress. The overexpression of in -depleted cells restored as well as antioxidant gene expression. In turn, Nrf2 regulated the expression of in the presence of oxidative stress. ChIP experiments showed that PICH is present on the as well as antioxidant gene promoters, suggesting that the protein might be regulating the expression of these genes directly by binding to the DNA sequences. In addition, Nrf2 and histone acetylation (H3K27ac) also played a role in activating transcription in the presence of oxidative stress. Both Nrf2 and H3K27ac were found to be present on and antioxidant promoters. Their occupancy was dependent on the expression as fold enrichment was found to be decreased in -depleted cells. PICH ablation led to the reduced expression of Nrf2 and impaired antioxidant response, leading to increased ROS content and thus showing PICH is essential for the cell to respond to oxidative stress.

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