Long non-coding RNA PARTICLE bridges histone and DNA methylation

Area of Science:

• Epigenetics
• Molecular Biology
• Radiation Biology

Background:

• PARTICLE (Promoter of MAT2A-Antisense Radiation Induced Circulating LncRNA) is a long non-coding RNA induced by low-dose radiation.
• This lncRNA was previously shown to repress its neighboring Methionine adenosyltransferase 2A gene via epigenetic silencer recruitment.

Purpose of the Study:

• To investigate the broader role of PARTICLE in epigenetic regulation beyond its neighboring gene.
• To elucidate the mechanism by which PARTICLE influences DNA and histone methylation.

Main Methods:

• Chromatin immunoprecipitation sequencing (ChIP-seq)
• Immunological assays
• Live-cell imaging (dbroccoli-PARTICLE)
• Flow cytometry
• Electrophoretic mobility shift assay (EMSA)

Main Results:

• Elevated PARTICLE expression correlates with increased histone 3 lysine 27 trimethylation.
• PARTICLE dynamically associates with DNA methyltransferase 1 (DNMT1).
• Direct binding interactions between PARTICLE and DNMT1 were confirmed.

Conclusions:

• PARTICLE functions as a trans-acting mediator of DNA and histone methylation.
• This lncRNA acts as a regulatory platform, integrating epigenetic modification pathways.
• PARTICLE is a novel component involved in large-scale gene silencing mechanisms.