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. 2021 May 21;11:93. doi: 10.1186/s13578-021-00611-7

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — KD increases NRG1 expression via histone acetylation. A Representative Western blots showing H3, H4 proteins and their acetylation levels in the hippocampus of CD or KD-fed mice. GAPDH serves as a loading control. B Quantitative analysis of data in A. n=4 mice per group. Students t test, for H3, t₍₆₎=0.2343, P=0.8225; for H3k18ac, t₍₆₎=0.9896, P=0.3606; for H3k27ac, t₍₆₎=3.816, P=0.0088; for H4, t₍₆₎=0.6188, P=0.5588; for H4k8ac, t₍₆₎=3.378, P=0.0149; for H4k12ac, t₍₆₎=4.479, P=0.0042. C Hippocampal samples from CD and KD groups were subjected to Chromatin Immunoprecipitation (CHIP). Shown was the CHIP procedure workflow. D Agarose gel electrophoresis of CHIP-qPCR products. E Increased level of H4 acetylation at Nrg1 promoter in KD-fed mice. n=4 mice per group. Students t test, t(6)=4.698, P=0.0033. F TSA treatment increased hippocampal Nrg1 mRNA level and diminished the difference between CD and KD groups. n=5 mice per group except that n=6 mice for CD+TSA group. Two-way ANOVA with sidaks multiple comparison tests. F_(1,17)=12.71, P=0.0024; CD+vehicle vs KD+vehicle, P=0.0008; CD+vehicle vs CD+TSA, P<0.0001; CD+TSA vs KD+TSA, P>0.9999. G NRG1 level in the hippocampus was increased by TSA treatment. Shown were representative western blot images. GAPDH serves as a loading control. H Quantitative analysis of western blot data in G. One-way ANOVA, for H3, F_(3,12)=0.4619, P=0.7141; for H3K27ac, F_(3,12)=15.9, P=0.0002. CD+vehicle vs KD+vehicle, P=0.0469; CD+vehicle vs CD+TSA, P=0.0004; CD+TSA vs KD+TSA, P>0.9999; for H4, F_(3,12)=0.5403, P=0.6637; for H4K12ac, F_(3,12)=17.86, P=0.0001. CD+vehicle vs KD+vehicle, P=0.0012; CD+vehicle vs CD+TSA, P=0.0003; CD+TSA vs KD+TSA, P>0.9999; For NRG1, F_(3,12)=29.81, P<0.0001. CD+vehicle vs KD+vehicle, P=0.0072; CD+vehicle vs CD+TSA, P<0.0001; CD+TSA vs KD+TSA, P=0.7846. * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001