title: Valproic acid-induced histone acetylation suppresses CYP19 gene expression and inhibits the growth and survival of endometrial stromal cells.
abstract: Endometriosis is a common type of estrogen‑dependent, gynecological and chronic inflammatory disease. Epigenetics refers to changes in gene expression that occur without altering the DNA sequence or DNA content. Histone modification dominates epigenetics, and histone acetylation is the most extensively studied type of histone modification. The CYP19 gene is the gene that encodes P450 aromatase, which regulates the synthesis of estrogen. Hence, we conducted this study to investigate whether histone acetylation has an effect on CYP19 expression and whether histone acetylation is related to endometrial stromal cells (ESCs). Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and chromatin immunoprecipitation assays were performed. The results revealed that valproic acid (VPA) significantly promoted histone acetylation in the ESCs, which inhibited histone acetylation in the promoter region of the CYP19 gene, thus suppressing its expression. We also noted that VPA inhibited cell viability and proliferation, and induced the apoptosis, of ESCs. The findings of our study on histone acetylation, endometriosis and the CYP19 gene provide insight which may aid in the research of histone acetylation and suggest that the CYP19 gene may be a novel therapeutic target and method for the treatment of endometriosis.
authors.affiliation: Department of Obstetrics and Gynaecology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynaecology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Shengyun
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Obstetrics and Gynaecology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynaecology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Xu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001141:Aromatase / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004715:Endometriosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D014635:Valproic Acid; D001141:Aromatase; C561410:CYP19A1 protein, human