Proc Natl Acad Sci USA.2017 ; 114(35):E7245-7254. doi:10.1073/pnas.1704155114. Epub 2017 Aug 14
Kinetic and high-throughput profiling of epigenetic interactions by 3D-carbene chip-based surface plasmon resonance imaging technology.
Zhao S1,2, Yang M3,4, Zhou W3,4, Zhang B1,2, Cheng Z3,4, Huang J1,2, Zhang M1,2, Wang Z3,4, Wang R3,4, Chen Z1,2, Zhu J5,4, Li H6,2.
Abstract
Chemical modifications on histones and DNA/RNA constitute a fundamental mechanism for epigenetic regulation. These modifications often function as docking marks to recruit or stabilize cognate "reader" proteins. So far, a platform for quantitative and high-throughput profiling of the epigenetic interactome is urgently needed but still lacking. Here, we report a 3D-carbene chip-based surface plasmon resonance imaging (SPRi) technology for this purpose. The 3D-carbene chip is suitable for immobilizing versatile biomolecules (e.g., peptides, antibody, DNA/RNA) and features low nonspecific binding, random yet function-retaining immobilization, and robustness for reuses. We systematically profiled binding kinetics of 1,000 histone "reader-mark" pairs on a single 3D-carbene chip and validated two recognition events by calorimetric and structural studies. Notably, a discovery on H3K4me3 recognition by the DNA mismatch repair protein MSH6 in Capsella rubella suggests a mechanism of H3K4me3-mediated DNA damage repair in plant.
Nat Chem Biol.2016;12(12):1111-1118. doi:10.1038/nchembio.2218. Epub 2016 Oct 24
Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.
Xiong X1, Panchenko T2, Yang S1, Zhao S1, Yan P1,3, Zhang W3,4, Xie W3,4, Li Y1,4, Zhao Y5, Allis CD2, Li H1,4,6.
Abstract
Recognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr. Crystal structures of the DPF domain of MOZ in complex with H3K14cr, H3K14bu, and H3K14pr peptides reveal that these non-acetyl acylations are anchored in a hydrophobic 'dead-end' pocket with selectivity for crotonylation arising from intimate encapsulation and an amide-sensing hydrogen bonding network. Immunofluorescence and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) showed that MOZ and H3K14cr colocalize in a DPF-dependent manner. Our studies call attention to a new regulatory mechanism centered on histone crotonylation readout by DPF family members.
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