library_construction_protocol: Total RNA was extracted from snap-frozen liver tissues using TRIzol (Invitrogen) followed by RNeasy Mini Kit (Qiagen). For RNA-seq, all samples were sequenced separately for three biological replicate. RNA integrity was examined using Agilent RNA 6000 Nano kit. RNA samples with RNA integrity number >7 (1 μg) were used for RNA cleanup, library preparation and sequencing by Novogene, Durham, NC. For MMI-treated mice, total RNA was prepared from frozen liver, using TRIzol Reagent (Invitrogen #15596-026), then mRNA enriched from 5 μg aliquots of total RNA using Dynabeads mRNA purification Kit (Ambion # 61006) and quantified using Qubit RNA Broad-range assay Kit (Thermo Fischer Scientific). Double-stranded cDNA was prepared using SuperScript Double- Stranded cDNA Synthesis Kit (Invitrogen) and cDNA libraries for sequencing were generated using ThruPLEX DNA-seq kit (Takara #R400428). Multiplex sequencing was performed, yielding single-end 50 base length reads, at the NIDDK Genomic Core using an Illumina HiSeq 2500 instrument. All RNA-seq experiments were performed with three biological replicates per condition.