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Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Apr 25; Vol. 22 (9). Date of Electronic Publication: 2021 Apr 25. - Publication Year :
- 2021
-
Abstract
- Proper regulation of sebum production is important for maintaining skin homeostasis in humans. However, little is known about the role of epigenetic regulation in sebocyte lipogenesis. We investigated histone acetylation changes and their role in key lipogenic gene regulation during sebocyte lipogenesis using the human sebaceous gland cell line SZ95. Sebocyte lipogenesis is associated with a significant increase in histone acetylation. Treatment with anacardic acid (AA), a p300 histone acetyltransferase inhibitor, significantly decreased the lipid droplet number and the expression of key lipogenic genes, including sterol regulatory-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). In contrast, treatment with trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, increased the expression of these genes. Global HDAC enzyme activity was decreased, and HDAC1 and HDAC2 expression was downregulated during sebaceous lipogenesis. Interestingly, HDAC1 knockdown increased lipogenesis through SREBP1 induction, whereas HDAC1 overexpression decreased lipogenesis and significantly suppressed SREBP1 promoter activity. HDAC1 and SREBP1 levels were inversely correlated in human skin sebaceous glands as demonstrated in immunofluorescence images. In conclusion, HDAC1 plays a critical role in reducing SREBP1 transcription, leading to decreased sebaceous lipogenesis. Therefore, HDAC1 activation could be an effective therapeutic strategy for skin diseases related to excessive sebum production.
- Subjects :
- Cell Line
Epigenesis, Genetic
Gene Expression Regulation
Histone Deacetylase 1 genetics
Histone Deacetylase 2 metabolism
Histones metabolism
Humans
Hydrocarbons, Fluorinated pharmacology
Insulin metabolism
Insulin pharmacology
Lipid Metabolism drug effects
Lipogenesis drug effects
Lipogenesis genetics
Liver X Receptors agonists
Sebaceous Glands metabolism
Skin cytology
Sterol Regulatory Element Binding Protein 1 metabolism
Sulfonamides pharmacology
Histone Deacetylase 1 metabolism
Lipogenesis physiology
Sebaceous Glands cytology
Sterol Regulatory Element Binding Protein 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33922983
- Full Text :
- https://doi.org/10.3390/ijms22094477