Impact of Germline Depletion of Bonus on Chromatin State in Drosophila Ovaries
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1.
California Institute of Technology
Abstract
Gene expression is controlled via complex regulatory mechanisms involving transcription factors, chromatin modifications, and chromatin regulatory factors. Histone modifications, such as H3K27me3, H3K9ac, and H3K27ac, play an important role in controlling chromatin accessibility and transcriptional output. In vertebrates, the Transcriptional Intermediary Factor 1 (TIF1) family of proteins play essential roles in transcription, cell differentiation, DNA repair, and mitosis. Our study focused on Bonus, the sole member of the TIF1 family in Drosophila, to investigate its role in organizing epigenetic modifications. Our findings demonstrated that depleting Bonus in ovaries leads to a mild reduction in the H3K27me3 level over transposon regions and alters the distribution of active H3K9ac marks on specific protein-coding genes. Additionally, through mass spectrometry analysis, we identified novel interacting partners of Bonus in ovaries, such as PolQ, providing a comprehensive understanding of the associated molecular pathways. Furthermore, our research revealed Bonus's interactions with the Polycomb Repressive Complex 2 and its co-purification with select histone acetyltransferases, shedding light on the underlying mechanisms behind these changes in chromatin modifications.
Copyright and License
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Acknowledgement
We thank members of the Aravin and Kulbachinskiy labs for discussion. We thank Andrey Kulbachinskiy, Maria Ninova, and Peiwei Chen for comments on the manuscript. We are grateful to the Bloomington Stock Center for providing fly stocks, and Hugo Bellen for providing the antibodies. We thank Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech) for help with sequencing, and Giada Spigolon (Biological Imaging Facility, Caltech) for help with microscopy.
Funding
This work was supported by grants from the National Institutes of Health (R01 GM097363 to A.A.A. and R01 GM110217 to K.F.T.) and by the HHMI Faculty Scholar Award to A.A.A.
Contributions
B.G. and A.A.A. conceptualized the study. B.G. designed and performed experiments, data curation, and formal analysis, except LC-MS runs and raw data processing, which were performed at the Caltech PEL facility by B.G., B.Q., T.-F.C. and B.G. prepared figures and drafted the manuscript. B.G., K.F.T. and A.A.A. edited the manuscript. All authors have read and agreed to the published version of the manuscript.
Data Availability
The data presented in this study are available from the corresponding author on reasonable request.
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cells12222629/s1, Figure S1: Average plot profiles of H3K27me3 (A), H3K27ac (B), and H3K9ac (C) over the gene body in control and Bon germline knockdown ovaries (BonusKD).
Conflict of Interest
The authors declare no conflict of interest.
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Additional details
- PMCID
- PMC10670193
- R01 GM097363
- National Institutes of Health
- R01 GM110217
- National Institutes of Health
- Howard Hughes Medical Institute
- Caltech groups
- Tianqiao and Chrissy Chen Institute for Neuroscience, Division of Biology and Biological Engineering