# Enhancer for UCP1 transcription and thermogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $578,060

## Abstract

Obesity, the accumulation of excess white adipose tissue (WAT), has become an epidemic and is
associated with chronic metabolic diseases, such as type 2 diabetes. While WAT serves primarily as an energy
storage organ, brown adipose tissue (BAT) dissipates energy by generating heat mainly via UCP1 for
maintenance of body temperature. Increasing BAT activity by activating UCP1 may promote energy
expenditure to combat obesity. We have been studying transcriptional activation of UCP1 and thermogenic
gene program and previously found two transcription factors, Zfp516 and Zc3h10 and recruitment of their
coregulators PRDM16/LSD1 and Dot1L, respectively, critical for activation of UCP1 and thermogenic program.
In continuing our efforts to understand UCP1 transcription, our recent ATAC-seq and 3C-based crosslinking
identified a potential new enhancer far upstream of UCP1 locus. We will study this region to act as an
enhancer by examining histone modification, UCP1 promoter activation, and eRNA production, as well as in
the genomic context by CRISPRa and CRISPRi. Moreover, we will examine the involvement of an associated
transcription factor for its enhancer function. Finally, we will assess the impact of this enhancer and the
transcription factor on thermogenesis, adiposity, and glucose/insulin homeostasis in vivo in mice. Overall,
elucidating the role of a previously uncharacterized far upstream UCP1 enhancer and the associated factor will
help us to fully understand UCP1 transcription and thus thermogenesis. Our studies may provide new
obesity/diabetes therapeutics in the future.
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## Key facts

- **NIH application ID:** 10945229
- **Project number:** 1R01DK140318-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Hei Sook Sul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $578,060
- **Award type:** 1
- **Project period:** 2024-09-10 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945229

## Citation

> US National Institutes of Health, RePORTER application 10945229, Enhancer for UCP1 transcription and thermogenesis (1R01DK140318-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10945229. Licensed CC0.

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