Fig. 3: SREBP2 regulates MMAB/MVK expression in vitro and in vivo.

a Schematic diagram of human chromosome 12, showing the localization of MMAB and MVK. The active promoter region of MMAB and MVK is shown in red (HepG2 ChromHMM) and correlates with CpG islands (green) and enriched H3K4Me3 marks. Transcription factor binding sites (as assayed by ChIP-seq) are shown below. SREBP2, SREBP1, SP1, and p300 are highlighted in red. Data were compiled using the UCSC Genome Browser (NCBI36/hg18, http://genome.ucsc.edu). b qRT-PCR analysis of SREBP2-responsive genes in Huh7 cells incubated in lipoprotein-deficient serum (LPDS), LPDS + 5 µM statin, or LPDS + 120 µg/ml native LDL (nLDL) for 24 h. Relative expression levels were normalized to those cells incubated in LPDS (dashed line). Data are mean ± s.e.m. of three independent experiments in duplicate. Statistical comparisons by two-way ANOVA with Bonferroni correction for multiple comparisons. c, d Representative Western blot of LDLR, SREBP2, and MMAB in Huh7 cells incubated in lipoprotein-deficient serum (LPDS), LPDS + 5 µM statin, or LPDS + 120 µg/ml native LDL (nLDL) for 24 h. HSP90 was used as a loading control. Quantification of blot shown in panel (d). Data are mean ± s.e.m. of three independent experiments. Statistical comparisons by two-way ANOVA with Bonferroni correction for multiple comparisons. e qRT-PCR analysis of SREBP2-responsive genes in the livers of C57BL/6 mice fed a chow diet, chow diet supplemented with statin (statin) or high-fat diet (HFD). Data are mean ± s.e.m. n = 6 mice per group. Statistical comparisons by two-way ANOVA with Bonferroni correction for multiple comparisons. f MMAB, MVK and LDLR promoter activity in Huh7 cells incubated in 20% FBS + 60 µg/ml native LDL (nLDL) or LPDS and 5 µM statin for 24 h (LPDS + statin). Data are mean ± s.e.m. of three independent experiments in triplicate. Statistical comparisons by two-sided unpaired Student’s t test. g MMAB and MVK promoter activity in HeLa cells transfected with an empty vector (–) or 0.5, 1, and 2 μg nuclear SREBP2 (nSRE2). Data are mean ± s.e.m. of six independent experiments in duplicate. Statistical comparisons by one-way ANOVA with Bonferroni correction for multiple comparisons. Source data are provided as a Source Data file.