Mecp2 S80 phosphorylation regulates gene expression in CCl 4 -induced liver fibrosis. (A) Gene expression variances between WT and Mecp2 S80A fibrotic livers displayed as PCA plots of scaled log2-transformed transcript counts. (B) Heatmap displaying results of transcriptome sequencing carried out using 3 CCl 4 -injured livers from each of the WT and Mecp2 S80A mice; genes with greater than 2-fold change and significant to P < .01 are shown. Green indicates negative values (downregulated in Mecp2 S80A ); red, positive (up-regulated in Mecp2 S80A ); black, unchanged. (C, D) IPA was used to form a network of focused genes that are downstream targets of differentially expressed RNAs. Blue nodes show down-regulated genes in Mecp2 S80A CCl 4 -injured liver; red nodes are up-regulated. Symbol shapes signify the nature of the encoded protein (see Supplementary Figures 1 and 2 for shape information), and unshaded symbols signify genes relevant to the pathway but not differentially expressed in our data set. signif diff, significantly different.

Contexts in source publication

Context 1

... These data encouraged us to examine the role of pMecp2 S80 in HSCs using primary cells isolated from digested livers of mutant Mecp2 S80A knock-in (S80A) mice. Although we were able to establish Mecp2 S80A HSC lines, they were morphologically observed to be more rounded (ie, less activated) and were slower growing than WT lines (Supplementary Figure 7); the reduced proliferative rate was confirmed by BrdU incorporation ( Figure 4B), and MTT assays were carried out across a time course of transdifferentiation ( Figure 4C). Moreover, S80A HSCs were impaired for expression of Mcm5 transcript and protein ( Figure 4D) and displayed diminished expression of CCNA2 and Brip1 ( Figure 4E). ...

Context 2

... the protective effect of S80A point mutation on fibrosis, we performed transcriptomic sequencing of CCl 4 -injured livers. Sequencing data from 2 groups were normalized and used to generate a PCA plot, which showed clear phenotypic differences between the WT and S80A ( Figure 7A). Interrogation of the sequencing data showed reduced expression of 116 genes and up-regulation of 306 genes in S80A livers compared with the WT ( Figure 7B and Supplementary Table 6). ...

Context 3

... data from 2 groups were normalized and used to generate a PCA plot, which showed clear phenotypic differences between the WT and S80A ( Figure 7A). Interrogation of the sequencing data showed reduced expression of 116 genes and up-regulation of 306 genes in S80A livers compared with the WT ( Figure 7B and Supplementary Table 6). IPA analysis of differentially expressed genes in S80A-injured livers showed similar networks to those identified in Mecp2 -/y myofibroblasts, particularly pathways involving histones H3 and H4, extracellular signal-regulated kinases 1 and 2, and RNA polymerase II ( Figure 7C and D and Supplementary Figures 1 and 2). ...

Context 4

... of the sequencing data showed reduced expression of 116 genes and up-regulation of 306 genes in S80A livers compared with the WT ( Figure 7B and Supplementary Table 6). IPA analysis of differentially expressed genes in S80A-injured livers showed similar networks to those identified in Mecp2 -/y myofibroblasts, particularly pathways involving histones H3 and H4, extracellular signal-regulated kinases 1 and 2, and RNA polymerase II ( Figure 7C and D and Supplementary Figures 1 and 2). These data suggest a role for S80 phosphorylation in controlling Mecp2-mediated regulation of chromatin structure and gene transcription as well as mitogenactivated protein kinase signaling cascades in hepatic myofibroblasts and liver fibrosis. ...