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Histone demethylase LSD1 regulates adipogenesis
Melina M Musri1, Mari Carmen Carmona, Felicia A Hanzu
1Endocrinology and Nutrition Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona 08036, Spain.
The Journal of Biological Chemistry
|July 27, 2010
Summary
Histone methylation regulates adipogenesis. The enzyme LSD1 maintains gene promoters in a receptive state, while SETDB1 opposes this, impacting cell differentiation.
Area of Science:
- Epigenetics
- Molecular Biology
- Cellular Differentiation
Background:
- Histone modifications, particularly histone methylation, are key to cell differentiation.
- Adipogenic gene promoters in preadipocytes show H3K4 dimethylation, maintaining a receptive chromatin state.
- Histone demethylase and methyltransferase expression changes during adipogenesis.
Purpose of the Study:
- Investigate the role of histone demethylases and methyltransferases in adipogenesis.
- Determine the function of LSD1 and SETDB1 in regulating adipogenic gene promoters.
- Elucidate the impact of histone methylation dynamics on 3T3-L1 preadipocyte differentiation.
Main Methods:
- Knockdown of histone-modifying enzymes (LSD1, SETDB1) in 3T3-L1 preadipocytes.
- Analysis of histone methylation marks (H3K4, H3K9 dimethylation) at the cebpa promoter.
- Assessment of adipocyte differentiation efficiency following enzyme knockdown.
Main Results:
- LSD1 knockdown decreased 3T3-L1 differentiation, reducing H3K4me2 and increasing H3K9me2 at the cebpa promoter.
- SETDB1 knockdown increased H3K4me2 and decreased H3K9me2 at the cebpa promoter, favoring differentiation.
- Dynamic changes in histone methylation and the enzymes regulating them are crucial for adipogenesis.
Conclusions:
- LSD1 maintains an open chromatin state at adipogenic promoters, opposing H3K9 methylation.
- SETDB1 promotes gene silencing via H3K9 methylation, counteracting adipogenic gene activation.
- Histone methylation dynamics orchestrated by LSD1 and SETDB1 are essential regulators of adipogenesis.
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