NAD+ sensing by PARP7 regulates the C/EBPβ-dependent transcription program during adipogenesis

  • Cell Rep. 2026 Feb 24;45(2):116929. doi: 10.1016/j.celrep.2026.116929.
MiKayla S Stokes  1 ,  Yoon Jung Kim  2 ,  Yonghyeon Kim  3 ,  Sneh Koul  3 ,  Shu-Ping Chiu  3 ,  Chenqian Liu  3 ,  Morgan Dasovich  3 ,  Josue Zuniga  3 ,  Tulip Nandu  3 ,  Dan Huang  4 ,  Thomas P Mathews  2 ,  Ashley Solmonson  5 ,  Cristel V Camacho  4 ,  W Lee Kraus  6
Affiliations
  • 1. The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Program in Genetics, Development and Disease, Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 2. Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3. The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 4. The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; The Section of Laboratory Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5. The Laboratory of Developmental Metabolism and Placenta Biology, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; The Section of Laboratory Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 6. The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Program in Genetics, Development and Disease, Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; The Section of Laboratory Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].
PMID: 41621069 DOI: 10.1016/j.celrep.2026.116929
Abstract

We identified poly(ADP-ribose) polymerase 7 (PARP7), a mono(ADP-ribosyl) transferase, as a regulator of C/EBPβ-dependent proadipogenic gene expression. PARP7 functions as a nuclear NAD+ sensor; at higher nuclear NAD+ concentrations in undifferentiated preadipocytes, PARP7 is catalytically active for auto-mono(ADP-ribosyl)ation (autoMARylation). As nuclear NAD+ concentrations decline upon differentiation, autoMARylation decreases dramatically. AutoMARylation promotes instability of PARP7 through an E3 ligase-ubiquitin-proteasome pathway mediated by the ubiquitin E3 Ligases DTX2 and RNF114, which ubiquitylate MARylated PARP7. Stabilized PARP7 serves as a coregulator of C/EBPβ by stimulating p300-mediated histone H3 lysine 27 acetylation and the binding of C/EBPβ across the genome. Genetic depletion of PARP7 in mice promotes decreased body weight in mice fed a high-fat diet, reduced fat mass, inhibition of adipogenesis during mammary gland involution, and a reduction in lipid synthesis. Collectively, our results extend the biology of PARP7 to adipogenesis and elucidate the molecular mechanisms underlying a PARP7-p300-H3K27ac-C/EBPβ pathway for proadipogenic gene regulation.

Keywords
ADP-ribosylation; C/EBPβ; CP: metabolism; CP: molecular biology; H3 lysine 27 acetylation; MART; NAD(+); PARP7; adipogenesis; mono(ADP-ribosyl)transferase; p300; transcription; ubiquitylation.
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