由H3K36me3调节的Epitranscriptomic阅读器,写入器和擦除器蛋白的有针对性的分析
Jiekai Yin1, Tianyu F Qi1, Lin Li2
1Environmental Toxicology Graduate Program, University of California, Riverside, California 92521-0403, United States.
Analytical chemistry
|June 9, 2023
概括
lysine 36 在 histone H3 (H3K36me3) 上的三甲基化会影响染色蛋白占用率和基因调节. 这项研究揭示了H3K36me3,H4K16ac和表皮转录蛋白之间的交叉对话,影响了癌症生物学.
科学领域:
- 表观遗传学和分子生物学
- 癌症研究 癌症研究
- 蛋白质组学是指蛋白质组学.
背景情况:
- 基因组H3 lysine 36三甲基化 (H3K36me3) 是一个关键的表观遗传标记,调节基因转录,DNA修复和甲基化.
- 主要的H3K36me3甲基转移酶SET域含有2 (SETD2) 因异常表达或突变而与各种癌症有关.
研究的目的:
- 为了研究H3K36me3对表表体转录体读者,写者和擦拭器 (RWE) 蛋白质的染色质占用量的影响.
- 探索细胞过程和癌症中的基因素标记和表皮转录机械之间的相互作用.
主要方法:
- 使用计划液体染色学并行反应监测 (LC-PRM) 对154种表转录体RWE蛋白进行向分析.
- 使用稳定同位素标记 (SIL) 作为定量分析的内部标准.
- 进行了蛋白质-蛋白质相互作用网络和卡普兰-梅尔生存分析.
主要成果:
- 在失去H3K36me3和H4K16ac.ac.后观察到RWE蛋白染色质占用量的一致变化.
- 在DNA双链断裂后,证明H3K36me3在招募METTL3到染色质中的作用.
- 确定了METTL14和TRMT11作为癌进展的重要因素.
结论:
- 揭示了基因组表观遗传标记 (H3K36me3,H4K16ac) 和表体转录RWE蛋白之间的显著交叉对话.
- 突出了RWE蛋白在H3K36me3介导的生物过程中的潜在作用.
- 强调了METTL14和TRMT11在癌中的临床相关性.
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