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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.
This article was published in the following journal.
Name: Nature cell biology
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The larger of two types of nuclei in ciliate protozoans. It is the transcriptionally active nucleus of the vegetative cells as distinguished from the smaller transcriptionally inert GERMLINE MICRONUCLEUS.
One of the PPAR nuclear transcription factors.
The smaller, reproductive, transcriptionally inert nucleus in the cells of ciliate protozoans, as distinguished from the larger, vegetative, transcriptionally active MACRONUCLEUS. Micronuclei participate in MEIOSIS and autogamy during GENETIC CONJUGATION.
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
A lipid droplet protein that is expressed primarily by ADIPOCYTES of WHITE ADIPOSE TISSUE and BROWN ADIPOSE TISSUE. It co-localizes with MACROPHAGES and FOAM CELLS of artherosclerotic lesions and stabilizes LIPID DROPLETS by inhibiting HORMONE SENSITIVE LIPASE. It may also protect TRIGLYCERIDES against hydrolysis within the PLASMA MEMBRANE and modulate CHOLESTEROL ESTER HYDROLASE activity.
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Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...