Fig. 7: MSI and tau bind Histone3 modulating chromatin state in the cells.
From: RNA-binding proteins Musashi and tau soluble aggregates initiate nuclear dysfunction
a, b H3K4me3 and H3K9me3 WB in cytoplasmic and nuclear fractions of WT and P301L tau iHEK. c Relative density of H3K4m3 in P301L (two-tailed unpaired t-test; Ctr vs Tet, * p = 0.0217) and WT iHEK (two-tailed unpaired t-test; p = 0.1758; ns). N = 3 biologically independent cells (ROIs) examined over three independent experiments. Data are presented as mean ± SD. d DAPI staining of nuclei control and TauO 0.5 µM treated P301L tau iHEK. Gray channel and LUT Fire are represented. White scale bar: 10 µm. e IB of Histone3, LaminB1, and GAPDH of IP MSI1 cytoplasm and nuclear fractions of control and Tet P301L tau iHEK. f IB of Histone3 and GAPDH of IP MSI2 nuclear fractions of control and Tet P310L tau iHEK. g IB of LaminA, LaminB1, Histone3, and GAPDH of IP Tau13 cytosolic and nuclear fractions of control and Tet P301L tau iHEK. All IB present Input (FT) fractions. h MS of IP TTC35 nuclear fraction of Histone proteins. i MS of IP MSI1 nuclear fraction of Histone proteins. j, k Normal and pathological, respectively, effects of mutant P301L tau oligomers in the cell model. Folded Monomeric tau and nuclear MSI1 regulate nuclear activity, while toxic tau conformers and nuclear MSI2 unbalanced nuclear homeostasis modulating chromatin remodeling, nucleoporin localization and destabilizing nuclear envelope.
