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Histone Demethylase LSD1 Regulates Adipogenesis
- Source :
- Journal of Biological Chemistry. 285:30034-30041
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Epigenetic mechanisms, in particular the enzymatic modification of histones, are a crucial element of cell differentiation, a regulated process that allows a precursor cell basically to turn into a different cell type while maintaining the same genetic equipment. We have previously described that the promoters of adipogenic genes display significant levels of dimethylation at the Lys4 of histone H3 (H3K4) in preadipocytes, where these genes are still silenced, thus maintaining the chromatin of the precursor cell in a receptive state. Here, we show that the expression of several histone demethylases and methyltransferases increases during adipogenesis, suggesting an important role for these proteins in this process. Knockdown of the H3K4/K9 demethylase LSD1 results in markedly decreased differentiation of 3T3-L1 preadipocytes. This outcome is associated with decreased H3K4 dimethylation and increased H3K9 dimethylation at the promoter of transcription factor cebpa, whose expression must be induced >200-fold upon stimulation of differentiation. Thus, our data suggest that LSD1 acts to maintain a permissive state of the chromatin in this promoter by opposing the action of a H3K9 methyltransferase. Knockdown of H3K9 methyltransferase SETDB1 produced the opposite results, by decreasing H3K9 dimethylation and increasing H3K4 dimethylation levels at the cebpa promoter and favoring differentiation. These findings indicate that the histone methylation status of adipogenic genes as well as the expression and function of the proteins involved in its maintenance play a crucial role in adipogenesis.
- Subjects :
- Cellular differentiation
Biochemistry
Epigenesis, Genetic
Histones
Mice
Histone H3
3T3-L1 Cells
Histone methylation
Adipocytes
Animals
Histone code
Gene Regulation
Protein Methyltransferases
Promoter Regions, Genetic
Molecular Biology
Histone Demethylases
Adipogenesis
biology
Stem Cells
Cell Differentiation
Oxidoreductases, N-Demethylating
Histone-Lysine N-Methyltransferase
Cell Biology
Molecular biology
Chromatin
Histone
Gene Knockdown Techniques
Histone methyltransferase
CCAAT-Enhancer-Binding Proteins
biology.protein
Demethylase
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....48ddd4653d4ee801fd4e158787540c4d