DNMT3L Interacts with Piwi and Modulates the Expression of piRNAs in Transgenic Drosophila

Abstract

Aim:

To explore the role of Piwi protein and piRNAs in DNMT3L-mediated epigenetic inheritance.

Materials & methods:

Transgenic Drosophila were used to examine the effect of ectopically expressed DNMT3L on the profile of piRNAs by sequencing of small RNAs.

Results & conclusion:

Our previous work showed accumulation and inheritance of epimutations across multiple generations in transgenic DNMT3L Drosophila. Here, we show interaction of DNMT3L with Piwi and a significant alteration in the piRNA profile across multiple generations in transgenic Drosophila. In the light of its interaction with histone H1, we propose that in addition to its role of modulating core histone modifications, DNMT3L allows for inheritance of epigenetic information through its collaboration with Piwi, piRNAs and histone H1.

Tweetable abstract

The interaction of DNMT3L with Piwi and histone H1 and a significant alteration in the piRNA profile in transgenic Drosophila ectopically expressing DNMT3L allows inheritance of epigenetic information across multiple generations.

Keywords::

• chromatin
• DNMT3L
• Drosophila
• epigenetic inheritance
• histone H1
• piRNA
• Piwi

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0405

Author contributions

S Khosla conceived and designed the experiments. R Rajeev performed the experiments and analyzed the RNAseq data. S Khosla and R Rajeev analyzed the data and wrote the manuscript. R Mishra provided all the Drosophila resources and helped in designing the Drosophila experiments in CCMB.

Acknowledgments

The authors acknowledge J Peng for providing vector containing Flag-Piwi for our experiments. They thank S Verma for assisting with fly experiments, and S Bhakt for helping out in developing the piRNA mapping tool for the particular gene locus in the study.

Financial disclosure

R Rajeev is the recipient of Junior and Senior Research Fellowships of the Department of Biotechnology and was registered with the Manipal University for his PhD degree. S Khosla is a JC Bose Fellow of the Department of Science and Technology, India and supported by grants from CSIR and DBT, Government of India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Drosophila crosses and experiments were performed in the RKM laboratory at CCMB as per approved Institutional Animal Ethics Committee guidelines.