Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis

Extracellular signaling and nutrient availability are major factors for cell fate decision. Responds to extracellular information requires metabolic alterations and differential gene expression. However, how cells integrate extracellular signals (e.g. hormones) and cellular metabolic status to coordinate transcriptional outcome is poorly understood. We hypothesized that fluctuations in nuclear nicotinamide adenine dinucleotide (NAD+) levels act as a signal to integrate cellular glucose metabolism and transcription program during adipocyte differentiation. To test this hypothesis, we performed RNA-seq on control, Nmnat1 and Parp1 knockdown 3T3-L1 cells during various time point of differentiation. Using RNA-seq over a time course of DMI induced differention of 3T3-L1 preadipocytes expressing control or Nmnat1 or Parp1 shRNA.