Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg

Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg

〔研究ノート〕卵巣摘除された慢性腎臓病モデルラットの骨代謝維持に 対する食餌アルギニンあるいは大豆イソフラボン抽出物 投与の有効性評価に関する基礎的研究

The present study was carried out to elucidate the protective effects of dietary L-arginine and soy isoflavone-extracted on the bone metabolism in the ovariectomized chronic kidney disease model rats.　　Nine-week-old female rats received 360mg/kg BW of adenine intragastrally for four consecutive days so that they would develop chronic kidney disease（CKD）. After six days of recovery, rats received ovariectomies（OVX）under anesthesia. A sham operation was carried out on another group of rats（group Intact）.　　Seven days after the OVX, the rats were given either a control diet（20％ casein protein diet（group CA）; 0.5％ L-arginine supplemented diet（group Arg）; or 0.20％ soy isoflavone-extracted supplemented diet（group IF）, 13g per day for 12 weeks. Rats in group Intact were, like group CA, given the control diet.　　The results were as follows: 1）Group CA developed moderate chronic kidney disease which was manifested as elevated kidney weight, increased serum creatinine, relatively lower creatinine clearance and reduced femoral-BMD than that of group Intact.2）The L-Arginine supplemented diet did not improve renal function and femoral BMD-loss. But, increased mRNA expression levels of IGF-1, BMP-2 and Osterix were observed in the femurs.3）Soy isoflavone-extracted supplemented diet had no preventative effects on BMD loss, although estrogen receptor-beta mRNA expression levels in the femurs were elevated.　　From these results, bone-protective functions of L-arginine via activation of osteoblast differentiation and bone formation process were suggested. Further investigation to clarify the efficacy of L-arginine-IGF-1 signal transduction on the bone metabolism is required to determine whether a therapy based on this approach can help people suffering from osteoporosis in CKD patients