Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95

• Published in: International journal of molecular sciences 2021-04, Vol.22 (9), p.4477
• Main Authors: Shin, Hye Sun, Lee, Yuri, Shin, Mi Hee, Cho, Soo Ick, Zouboulis, Christos C, Kim, Min Kyoung, Lee, Dong Hun, Chung, Jin Ho
• Format: Article
• Language: English
• Subjects: Acetyl-CoA carboxylase; Acetylation; Acne; Adipocytes; Biosynthesis; Cell Line; Cholesterol; Enzymatic activity; Enzyme activity; Epigenesis, Genetic; Epigenetics; Fatty acids; Fatty-acid synthase; Gene expression; Gene Expression Regulation; Gene regulation; Genes; HDAC2 protein; histone acetylation; Histone acetyltransferase; Histone deacetylase; histone deacetylase 1; Histone Deacetylase 1 - genetics; Histone Deacetylase 1 - metabolism; Histone Deacetylase 2 - metabolism; Histones; Histones - metabolism; Homeostasis; Humans; Hydrocarbons, Fluorinated - pharmacology; Immunofluorescence; Inhibitors; Insulin; Insulin - metabolism; Insulin - pharmacology; Lipid Metabolism - drug effects; Lipids; Lipogenesis; Lipogenesis - drug effects; Lipogenesis - genetics; Lipogenesis - physiology; Liver X Receptors - agonists; Protein expression; Proteins; Sebaceous gland; Sebaceous glands; Sebaceous Glands - cytology; Sebaceous Glands - metabolism; sebocytes; sebum; Skin - cytology; Skin diseases; SREBP1; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Sulfonamides - pharmacology; Transcription; Trichostatin A; Triglycerides
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22094477

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 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.