Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
Cells. 2023 Nov 15;12(22):2629. doi: 10.3390/cells12222629.
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 , 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.
基因表达受转录因子、染色质修饰和染色质调节因子等复杂调控机制的控制。组蛋白修饰，如 H3K27me3、H3K9ac 和 H3K27ac，在控制染色质可及性和转录输出方面发挥着重要作用。在脊椎动物中，转录中介因子 1（TIF1）家族蛋白在转录、细胞分化、DNA 修复和有丝分裂中发挥着重要作用。我们的研究集中在 Bonus 上，这是 TIF1 家族在 中的唯一成员，以研究其在组织表观遗传修饰中的作用。我们的研究结果表明，在卵巢中耗尽 Bonus 会导致转座子区域的 H3K27me3 水平轻度降低，并改变特定蛋白编码基因上活性 H3K9ac 标记的分布。此外，通过质谱分析，我们在卵巢中鉴定到 Bonus 的新的相互作用伙伴，如 PolQ，从而全面了解相关的分子途径。此外，我们的研究揭示了 Bonus 与 Polycomb 抑制复合物 2 的相互作用及其与选定的组蛋白乙酰转移酶的共纯化，阐明了这些染色质修饰变化背后的潜在机制。
