Histones cause aggregation and fusion of lipid vesicles containing phosphatidylinositol-4-phosphate

In a previous article, we demonstrated that histones (H1 or histone octamers) interact with negatively charged bilayers and induce extensive aggregation of vesicles containing phosphatidylinositol-4-phosphate (PIP) and, to a lesser extent, vesicles containing phosphatidylinositol (PI). Here, we found that vesicles containing PIP, but not those containing PI, can undergo fusion induced by histones. Fusion was demonstrated through the observation of intervesicular mixing of total lipids and inner monolayer lipids, and by ultrastructural and confocal microscopy studies. Moreover, in both PI- and PIP-containing vesicles, histones caused permeabilization and release of vesicular aqueous contents, but the leakage mechanism was different (all-or-none for PI and graded release for PIP vesicles). These results indicate that histones could play a role in the remodeling of the nuclear envelope that takes place during the mitotic cycle.
This work was supported in part by grants from the Spanish Ministry of Economy (BFU 2011-28566 to A.A., BFU 2012-36241 to F.M.G., and BIO 2013-42978-P to M.M.) and the Basque Government (IT 838-13 and IT 849-13). M.G.L. was a predoctoral student supported by the Basque Government.