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Identify transcriptional regulators of Mc4r in the hypothalamus [ATAC-Seq]

GSE244790 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/01/15 Platform GPL24247
Summary
Human MC4R mutations can increase or decrease obesity risk. Other than intracellular signaling, MC4R function is also influenced by its levels. However, the genetic programs that govern MC4R transcription in the brain remain largely unknown. Moreover, it is unclear whether human genetic variants exist that affect Mc4r expression and obesity risk. Here, we identify the homeodomain transcription factor Otp as one regulator of Mc4r expression in a specific subset of hypothalamic neurons. Selective loss of Otp in these neurons during development or adulthood results in reduced Mc4r expression and excessive body weight gain. Moreover, OTP interacts with upstream regulatory sequences of Mc4r to modulate its transcription.
Published in
Orthopedia regulates melanocortin 4 receptor transcription and energy homeostasis
Xu B, Lawler K, Wyler SC et al. · Science translational medicine 2025 · PMID 39813316 · doi:10.1126/scitranslmed.adr6459
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Also filed as BioProject PRJNA1024902 and SRA study SRP464858. Searching any of these in the dataset finder brings you back here.

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