Lee, Ho-Youl Yang, Eun Gyeong Park, Hyunsung 2024-01-20T11:01:50Z 2024-01-20T11:01:50Z 2021-09-05 2013-12 0143-3334 https://pubs.kist.re.kr/handle/201004/127370 Oxygen concentration in prostate cancer tissue is significantly low, i.e. similar to 0.3% O-2. This study showed that pathological hypoxia (<0.5% O-2) increased the expression of androgen receptor (AR) target genes such as prostate-specific antigen (PSA) and kallikrein-related peptidase 2 in LNCaP human prostate cancer cells by modifying the quantity and activity of related Jumonji C domain-containing histone demethylases (JMJDs). Under pathological hypoxia, the catalytic activities of JMJD2A, JMJD2C and Jumonji/ARID domain-containing protein 1B (JARID1B) were blocked due to the lack of their substrate, i.e. oxygen. Chromatin immunoprecipitation analyses showed that hypoxia increased the appearance of H3K9me3 and H3K4me3, substrates of JMJD2s and JARID1B, respectively, in the PSA enhancer. In contrast, JMJD1A, which demethylates both H3K9me2 and H3K9me1, maintained its catalytic activity even under severe hypoxia. Furthermore, hypoxia increased the expression of JMJD1A. Hypoxia and androgen additively increased the recruitment of JMJD1A and p300 on the enhancer region of PSA through interaction with the hypoxia-inducible factor-1 alpha and AR, both of which bind the PSA enhancer. Thus, hypoxia enhanced the demethylation of H3K9me2 and H3K9me1, leading to provide unmethylated H3K9 residues that are substrates for histone acetyltransferase, p300. Consequently, hypoxia increased the acetylation of histones of the PSA enhancer, which facilitates its transcription. English OXFORD UNIV PRESS ANDROGEN RECEPTOR ACTIVATION DEPENDENT GENE-EXPRESSION METHYLTRANSFERASE G9A INDUCIBLE FACTORS JMJD2 FAMILY H3 LYSINE-9 TRANSCRIPTION CHROMATIN CANCER PHOSPHORYLATION Hypoxia enhances the expression of prostate-specific antigen by modifying the quantity and catalytic activity of Jumonji C domain-containing histone demethylases Article 10.1093/carcin/bgt256 1 CARCINOGENESIS, v.34, no.12, pp.2706 - 2715 CARCINOGENESIS 34 12 2706 2715 scie scopus 000328278900003 2-s2.0-84888997571 Oncology Oncology Article ANDROGEN RECEPTOR ACTIVATION DEPENDENT GENE-EXPRESSION METHYLTRANSFERASE G9A INDUCIBLE FACTORS JMJD2 FAMILY H3 LYSINE-9 TRANSCRIPTION CHROMATIN CANCER PHOSPHORYLATION