Role of Transcriptional Elongation in Dermal Fat Development

July 2025 in “ Journal of Investigative Dermatology ”

Souvik Mahapatra, Yong Chen, José Gregorio Cabrera Gómez, Celia Fernández-Méndez, Uyanga Batzorig, Y. Liu, George L. Sen

transcriptional elongation dermal white adipose tissue negative elongation factor PDGFRA+ dermal fibroblasts Nelfb adipogenesis Pparg Cebpa Krox20 Stat3 chromatin closure PPARG agonist Rosiglitazone PPAR gamma PPAR gamma agonist

TLDR Nelfb is essential for dermal fat development and survival.

The study investigates the role of transcriptional elongation in dermal white adipose tissue (dWAT) development, focusing on the function of the negative elongation factor (NELF) in PDGFRA+ dermal fibroblasts. By generating Nelfb deficient mice, researchers found that the absence of Nelfb led to a lack of dermal fat formation, perinatal lethality, and reduced expression of adipogenic regulators. Nelfb is crucial for adipogenesis as it binds to the transcription start sites of key genes like Pparg, Cebpa, Krox20, and Stat3, promoting their expression. The loss of Nelfb results in chromatin closure and silencing of these genes. However, retroviral expression of Pparg or treatment with the PPARG agonist Rosiglitazone in Nelfb deficient mice restored dWAT formation and increased lifespan, underscoring Nelfb's essential role in regulating adipogenesis and dWAT development.

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