An Integrated Approach Based on a DNA Self-Assembly Technique for Characterization of Crosstalk among Combinatorial Histone Modifications

Analytical Chemistry
Xue BaiKai Zhang

Abstract

Combinatorial histone post-translational modifications (HPTMs) form a complex epigenetic code that can be decoded by specific binding proteins, termed as readers. Their specific interplays have been thought to determine gene expression and downstream biological functions. However, it is still a big challenge to analyze such interactions due to various limitations including rather weak, transient, and complicated interactions between HPTMs and readers, the high dynamic property of HPTMs, and the low abundance of reader proteins. Here we sought to take advantage of DNA-templated and photo-cross-linking techniques to design a group of combinatorial histone PTM peptide probes for the identification of multivalent interactions among histone PTMs and readers. By use of trimethylation on histone H3K4 (H3K4me3) and phosphorylation on H3T3, we demonstrated that this approach can be successfully utilized for identification of the PTM crosstalk on the same histone. By use of H3K4me3 and acetylation on H4K16, we showed the potential application of the probe in the multivalent interactions among PTMs on different histones. Thus, this new chemical proteomics tool combined with mass spectrometry holds a promising potential in profiling of the...Continue Reading

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Citations

May 20, 2020·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Kenzo FujimotoShigetaka Nakamura
Mar 3, 2020·Frontiers in Bioengineering and Biotechnology·Qiuyun XiaoHai Xiong
Feb 11, 2021·The Biochemical Journal·Bethany C Taylor, Nicolas L Young
Apr 16, 2021·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Kenzo FujimotoShigetaka Nakamura

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