Related Experiment Video
Updated: Jun 4, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Stem cell protein Piwil2 modulates chromatin modifications upon cisplatin treatment
Qi-En Wang1, Chunhua Han, Keisha Milum
1Department of Radiology, The Ohio State University, Columbus, OH 43210, USA. wang.771@osu.edu
Mutation Research
|February 12, 2011
Summary
Piwil2 (mili) is crucial for DNA repair and sensitivity to cisplatin chemotherapy. Its overexpression in cancer may cause cisplatin resistance by altering chromatin structure and hindering DNA repair mechanisms.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Piwil2 (PIWI-interacting RNA 2), also known as mili in mice and hili in humans, is a PIWI/Argonaute family member involved in stem cell maintenance and gene silencing.
- Elevated Piwil2 expression in pre-cancerous cells and tumors suggests a role in tumorigenesis.
- Cisplatin is a widely used chemotherapy drug that induces DNA damage.
Purpose of the Study:
- To investigate the role of Piwil2 (mili) in cellular response to cisplatin treatment.
- To determine if Piwil2 influences chromatin modifications, DNA repair, and cisplatin sensitivity.
- To explore the potential link between Piwil2 overexpression and cisplatin resistance in ovarian cancer.
Main Methods:
- Comparison of cisplatin-induced chromatin relaxation and histone acetylation in wild-type (WT) and Piwil2-knockout (KO) mouse embryonic fibroblasts (MEFs).
- Analysis of histone acetyltransferase (HAT) p300 levels and activity in response to cisplatin.
- Assessment of DNA damage repair efficiency and cisplatin sensitivity in Mili-WT, Mili-KO MEFs, and cisplatin-resistant ovarian cancer cell lines with and without Piwil2 knockdown.
Main Results:
- Cisplatin induced chromatin relaxation and H3 hypoacetylation in Mili-WT MEFs, but not in Mili-KO MEFs, indicating Piwil2's role in maintaining euchromatin marks.
- Piwil2 deficiency (Mili-KO) resulted in reduced p300 HAT activity, impaired DNA damage repair, and increased sensitivity to cisplatin.
- Piwil2 was upregulated in cisplatin-resistant ovarian cancer cells; its knockdown sensitized these cells to cisplatin and reduced their ability to repair cisplatin-induced DNA intrastrand crosslinks (Pt-GG).
Conclusions:
- Piwil2 is essential for maintaining chromatin structure and facilitating DNA repair in response to cisplatin treatment.
- Overexpression of Piwil2 in certain cancers can confer cisplatin resistance by promoting chromatin condensation, which may impede DNA repair.
- Targeting Piwil2 could be a potential strategy to overcome cisplatin resistance in cancer therapy.
Related Concept Videos
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...