O-29: Aberrant Methylation of Lysine 9 on Histone 3 in PII Promoter of CYP19A1 Gene in Women with Endometriosis
Cytochrome aromatase p450, encoded by the gene CYP19A1, is a key enzyme for estrogen biosynthesis. Among the multiple promoters of CYP19A1, the proximal promoter PII is the most active ones in ovary and endometrium. Endometriosis is a chronic estrogen dependent gynecological condition characterized by the presence of ectopic glands and stroma outside the uterine cavity. Recently, evidence has emerged that endometriosis is an epigenetic disease. Thus, in the current work, the expression and epigenetic alteration of CYP19A1 were aimed to study.
Materials and methods
Epigenetic analysis of PII promoter of CYP19A1 was assayed by chromatin immunoprecipitation (CHIP), using anti-methylated histone 3 (H3K9Me2) antibody. Also, quantitative expression analysis of this gene was performed by real-time PCR technique. To this end, ectopic lesions and eutopic endometrium samples were collected using laparoscopy from 10 women with documented endometriosis. As a control group, endometrial tissues were collected from 10 healthy fertile women who underwent laparoscopy for tubal ligation surgery during menstrual cycle. Informed consent was collected from each participant.
Our finding showed that the methylation level of H3K9me2 in promoter PII decreased in eutopic endometrium in proliferative phase and increased in secretory phase in patients vs. control group. Furthermore, the gene expression profile was the inverse of this suppressive epigenetic mark. However, incorporation of H3K9me2 and mRNA expression of CYP19A1 in ectopic endometrial tissues was higher in both phases versus control group.
These results show an epigenetic switch between PII promoter of CYP19A1 gene in endometrial and endometriotic tissue of patients with endometriosis. Aberrant histone methylation may play a role in progression of endometriosis and support the opinion that epigenetic abnormalities have causative function in endometriosis. Therefore, it is suggested to investigate the epigenetic alteration of other promoters correlated with this gene in patients with endometriosis.