HRP2-MINA complex reprograms t(4;14) multiple myeloma epigenome to dictate chemosensitivity to proteasome inhibitors [ChIP-Seq]

Changes in these genes are probably a consequence of aging, and the real regulators governing BMSC senescence and osteogenesis are still unclear.In the current study, we report that nucleosome assembly-related protein NAP1L2 serves as an important regulator of both the senescence and osteogenic differentiation of BMSCs through inhibition of NF-?B signaling and recruitment of SIRT1 to deacetylate the H3K14ac level on promoters of osteogenic genes. Thus, targeting NAP1L2 using an aging antagonist such as NMN would benefit aging-related disease. Overall design: Examination of histone modification in non-target control and knockdown HRP2 LP-1 cells and HRP2 modification in LP-1 cells

这些基因的改变大概率是衰老的继发效应，而真正调控骨髓间充质干细胞（Bone Marrow Mesenchymal Stem Cells, BMSC）衰老与成骨过程的核心调控因子仍未明确。
本研究表明，核小体组装相关蛋白NAP1L2（nucleosome assembly-related protein NAP1L2）可通过抑制核因子κB（Nuclear Factor kappa B, NF-κB）信号通路，并招募沉默信息调节因子1（Sirtuin 1, SIRT1）对成骨基因启动子区域的组蛋白H3第14位赖氨酸乙酰化（Histone H3 Lysine 14 Acetylation, H3K14ac）水平进行脱乙酰化修饰，从而同时调控BMSCs的衰老与成骨分化，是一类关键调控因子。
据此，利用烟酰胺单核苷酸（Nicotinamide Mononucleotide, NMN）这类衰老拮抗剂靶向调控NAP1L2，将有望为衰老相关疾病的防治提供新思路。
实验整体设计：检测非靶向对照LP-1细胞、HRP2敲低LP-1细胞中的组蛋白修饰情况，以及LP-1细胞中的HRP2修饰状态。