Histone modifications associated with the histone chaperone DAXX

A multitude of histone chaperones is required to protect histones from their biosynthesis to DNA deposition. They cooperate through the formation of co-chaperone complexes, but the crosstalk between nucleosome assembly pathways is unclear. Using explorative interactomics approaches, we map the organization of the histone H3-H4 chaperones network and define the interplay between histone chaperones systems. We identify and validate a panel of novel histone (PTM) dependent complexes. We show DAXX acts separately from the rest of the network, recruiting heterochromatin factors and promoting lysine 9 tri-methylated new histone H3.3 prior to deposition onto DNA. With its functionality, DAXX provides a molecular mechanism for de novo heterochromatin assembly.

组蛋白从生物合成到DNA沉积的全过程，需要多种组蛋白伴侣（histone chaperones）的参与。这类蛋白通过形成共伴侣复合物（co-chaperone complexes）发挥协同作用，但目前核小体组装通路之间的相互串扰机制仍不明确。本研究借助探索性相互作用组学（interactomics）技术，绘制了组蛋白H3-H4伴侣网络的组织架构，并明确了不同组蛋白伴侣系统间的相互作用。我们鉴定并验证了一组依赖于组蛋白翻译后修饰（Post-translational modification，PTM）的新型复合物。研究发现，DAXX独立于该网络的其余部分发挥功能，可招募异染色质因子，并在新合成的组蛋白H3.3沉积至DNA之前，介导其赖氨酸9位点的三甲基化修饰。凭借这一功能，DAXX为从头异染色质组装提供了分子机制层面的解释。