The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key component of nuclear receptor-dependent transcription. Herein, we report the identification of several factors that associate with SETD6 and are implicated in nuclear hormone receptor signaling. Specifically, SETD6 associates with the estrogen receptor α (ERα), histone deacetylase HDAC1, metastasis protein MTA2, and the transcriptional co-activator TRRAP. Luciferase reporter assays identify SETD6 as a transcriptional repressor, in agreement with its association with HDAC1 and MTA2. However, SETD6 behaves as a co-activator of several estrogen-responsive genes, such as PGR and TFF1. Consistent with these results, silencing of SETD6 in several breast carcinoma cell lines induced cellular proliferation defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and induction of apoptosis. Herein, we have identified several chromatin proteins that associate with SETD6 and described SETD6 as an essential factor for nuclear receptor signaling and cellular proliferation.

Swyer syndrome is caused by abnormal sex differentiation during the embryonic period, resulting in incomplete intrauterine masculinization and undifferentiated gonads. The current case report describes a patient with Swyer syndrome associated with stage 3 gonadal dysgerminoma who has survived for 23 years. At age 18, this patient sought assistance for primary amenorrhea from the Gynecological Services Department of the University of Brasília Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect to axillary hair, breasts, and pubic hair; she presented with a eutrophic vagina and a small cervix. She was treated with a combination of estrogens and progestogens to induce cycling. Approximately 4 years later, a complex tumor was found and resected; a histopathological analysis revealed that this tumor was a right adnexal dysgerminoma with peritoneal affection. The patient was also subjected to chemotherapy. Her follow-up has continued to the present time, with no signs of tumor recurrence. In conclusion, this report describes an extremely rare case in which Swyer syndrome was associated with ovarian dysgerminoma; relative to similar patients, the described patient has survived for an unusually prolonged time.