Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95
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 lipogen...
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doaj-3e05636749bf44a8bbe4ace9b557e2892021-04-25T23:01:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01224477447710.3390/ijms22094477Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95Hye Sun Shin0Yuri Lee1Mi Hee Shin2Soo Ick Cho3Christos C. Zouboulis4Min Kyoung Kim5Dong Hun Lee6Jin Ho Chung7Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDessau Medical Center, Departments of Dermatology, Venereology, Allergology and Immunology, Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 06847 Dessau, GermanyDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaProper 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 <i>SREBP1</i> 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.https://www.mdpi.com/1422-0067/22/9/4477histone deacetylase 1SREBP1lipogenesissebocytessebumhistone acetylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hye Sun Shin Yuri Lee Mi Hee Shin Soo Ick Cho Christos C. Zouboulis Min Kyoung Kim Dong Hun Lee Jin Ho Chung |
spellingShingle |
Hye Sun Shin Yuri Lee Mi Hee Shin Soo Ick Cho Christos C. Zouboulis Min Kyoung Kim Dong Hun Lee Jin Ho Chung Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95 International Journal of Molecular Sciences histone deacetylase 1 SREBP1 lipogenesis sebocytes sebum histone acetylation |
author_facet |
Hye Sun Shin Yuri Lee Mi Hee Shin Soo Ick Cho Christos C. Zouboulis Min Kyoung Kim Dong Hun Lee Jin Ho Chung |
author_sort |
Hye Sun Shin |
title |
Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95 |
title_short |
Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95 |
title_full |
Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95 |
title_fullStr |
Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95 |
title_full_unstemmed |
Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95 |
title_sort |
histone deacetylase 1 reduces lipogenesis by suppressing srebp1 transcription in human sebocyte cell line sz95 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
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 <i>SREBP1</i> 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. |
topic |
histone deacetylase 1 SREBP1 lipogenesis sebocytes sebum histone acetylation |
url |
https://www.mdpi.com/1422-0067/22/9/4477 |
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