Nickel-induced transcriptional changes persist  post exposure through epigenetic reprogramming

Area of Science:

• Toxicology
• Epigenetics
• Molecular Biology

Background:

• Nickel is an occupational and environmental toxicant linked to human diseases like lung cancer.
• Previous studies indicated persistent genome-wide transcriptional changes after nickel exposure, but mechanisms were unclear.

Purpose of the Study:

• To investigate the mechanisms behind nickel-induced long-term transcriptional changes.
• To examine transcriptome and epigenome alterations in human lung cells during and after nickel exposure.

Main Methods:

• Analysis of transcriptome and epigenome in human lung epithelial cells.
• Identification of differentially expressed genes during and after nickel exposure.
• Assessment of histone modifications (H3K4me3 and H3K27me3) post-exposure.

Main Results:

• Two categories of persistently differentially expressed genes were identified: during exposure and after exposure.
• >85% of nickel-induced gene expression changes occurred only after nickel removal.
• Extensive genome-wide alterations in H3K4me3 and H3K27me3 were observed post-exposure, coinciding with gene expression changes.

Conclusions:

• Nickel exposure triggers a modest initial wave of transcriptional changes, followed by a significant second wave after nickel removal.
• The study uncovers a novel category of transcriptional and epigenetic changes occurring post-nickel exposure.
• This provides a new understanding of the long-term health consequences of nickel exposure.