Liver-specific matrin-3 knockout alters the chromatin accessibility in the liver of mice [ATAC-seq]

Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined its previously uncharacterized role in regulating chromatin accessibility in the liver of mice. Bulk ATAC-seq and bioinformatics analysis identified 523 and 829 differential peaks (FDR < 0.05), respectively, in the liver of female mice fed a chow diet or 60% HFD for 16 weeks. Peak annotation by HOMER and ChIPseeker identified 183 and 444 genes, respectively, that are associated with the differential peaks. Enrichr analysis of these genes revealed that Hallmark terms such as "Xenobiotic metabolism" was enriched in the liver of chow-fed and HFD-fed mice. TRRUST database analysis from Metascape uncovered that Hnf4α is the main transcription factor regulating these peak-associated genes in the liver of chow-fed mice, and Hnf4α and Nr1i3 are the main transcription factors regulating these peak-associated genes in the liver of HFD-fed mice. Our data demonstrated that liver-specific matrin-3 deficiency alters chromatin accessibility likely affecting the action of two transcription factors Hnf4α and Nr1i3 in the liver of mice. Matrin-3 floxed mice were bred with Albumin-Cre mice (The Jackson Laboratory, #003574) to produce liver-specific matrin-3 knockout mice (LKO). Mice were housed on a normal 12/12 light-dark cycle. Mice had ad libitum access to a normal chow diet (Envigo, cat# 2016) and water, or a HFD with 60 kcal% fat (Research Diets, D12492) and water. Female matrin-3 floxed mice and littermate LKO mice were fed a HFD at 7 weeks of age for 16 weeks. Sixteen weeks post-HFD, mice were fasted for 12 hours for euthanasia and tissue collection. Nuclei from 50 mg frozen liver were isolated following the Chang Lab protocol (Corces et al, 2017; PMID: 28846090) for ATACseq library construction.