Abstract
Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the master transcriptional regulator of adipogenesis, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts results in brown adipocyte differentiation. Conversely, the brown fat of NFIA-knockout mice displays impaired expression of the brown-fat-specific genes and reciprocal elevation of muscle genes. Finally, expression of NFIA and the brown-fat-specific genes is positively correlated in human brown fat. These results indicate that NFIA activates the cell-type-specific enhancers and facilitates the binding of PPARγ to control the brown fat gene program.
Original language | English |
---|---|
Journal | Nature Cell Biology |
Volume | 19 |
Issue number | 9 |
Pages (from-to) | 1081-1092 |
Number of pages | 12 |
ISSN | 1465-7392 |
DOIs | |
Publication status | Published - Sept 2017 |
Keywords
- 3T3-L1 Cells
- Adipocytes, Brown
- Adipogenesis
- Adipose Tissue, Brown
- Animals
- Binding Sites
- Chromatin
- DNA-Binding Proteins
- Enhancer Elements, Genetic
- Gene Expression Regulation
- Genotype
- High-Throughput Nucleotide Sequencing
- Mice
- Mice, 129 Strain
- Mice, Inbred C57BL
- Mice, Knockout
- Muscle Development
- Myoblasts
- NFI Transcription Factors
- PPAR gamma
- Phenotype
- Protein Binding
- RNA Interference
- Signal Transduction
- Time Factors
- Transcription Factors
- Transcription, Genetic
- Transfection
- Journal Article