title: Inhibition of DNA Methylation in the COL1A2 Promoter by Anacardic Acid Prevents UV-Induced Decrease of Type I Procollagen Expression.
abstract: UV radiation decreases type I procollagen production mainly by inhibiting the transforming growth factor-β/Smad signaling pathway. Because further epigenetic regulatory mechanisms are unclear, we investigated the roles of DNA methylation and histone acetylation in UV-induced regulation of COL1A2 transcription in human dermal fibroblasts. Anacardic acid, a p300 histone acetyltransferase inhibitor, rescued the UV-induced decrease of type I procollagen expression in human dermal fibroblasts. Although UV irradiation induced global histone acetylation, it reduced the local recruitment of histone H3 acetylation as well as p300, and Smad2/3 to the p300 binding site (-1406/-1393), in the COL1A2 promoter as shown by chromatin immunoprecipitation. This effect was reversed by anacardic acid treatment. In contrast, pyrosequencing analysis showed that UV irradiation induced DNA methylation in the same region of the COL1A2 promoter, which was reversed by anacardic acid and a DNA methyltransferase inhibitor (5-AZA-2'-deoxycytidine). Inhibition of UV-induced DNA methylation led to an increase of UV-induced histone acetylation in the COL1A2 promoter and increased the recruitment of transcription factors, leading to up-regulation of type I collagen after UV irradiation. Collectively, our findings indicate that the epigenetic crosstalk between DNA methylation and histone acetylation plays a crucial role in COL1A2 transcription induced by UV irradiation.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Shin
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea. Electronic address: ivymed27@snu.ac.kr.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Republic of Korea; Institute on Aging, Seoul National University, Seoul, Republic of Korea. Electronic address: jhchung@snu.ac.kr.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000107:Acetylation; D048729:Anacardic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024042:Collagen Type I / Q000235:genetics* / Q000528:radiation effects; D019175:DNA Methylation / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D048729:Anacardic Acids; C000601279:COL1A2 protein, human; D024042:Collagen Type I; D004268:DNA-Binding Proteins; D006657:Histones; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human