Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2007 Jul;31(1):219-23.
Epigenetic modifications of genomic DNA and histones alter the chromatin structure to regulate the accessibility of transcription factors to the promoter or enhancer regions. In 2003, we identified and characterized JMJD1C (TRIP8) consisting of TRI8H1 domain with C2HC4-type zinc finger-like motif, TRI8H2 domain with thyroid hormone receptor beta-binding region, and JmjC domain. JMJD1A (TSGA), JMJD1B (5qNCA) and JMJD1C with the common domain architecture are histone H3K9 demethylases implicated in the nuclear hormone receptor-based transcriptional regulation. Here, comparative integromics on JMJD1C gene is reported. JMJD1C variant 1, previously reported, consists of exons 1, 2 and 3-26, while JMJD1C variant 2 characterized in this study was transcribed from novel exon 1B located 5' to exon 3. Four human JMJD1C ESTs were transcribed from exon 1, while 14 human JMJD1C ESTs from exon 1B. All of 26 mouse Jmjd1c ESTs were transcribed from exon 1b. These facts indicate that JMJD1C variant 2 transcribed from exon 1B was the major transcript. Human JMJD1C variant 2 with TRI8H1, TRI8H2, and JmjC domains showed 85.7% total-amino-acid identity with mouse Jmjd1c. Human JMJD1C mRNA was expressed in undifferentiated embryonic stem (ES) cells, pancreatic islet, diffuse-type gastric cancer, and other tissues or tumors. Mouse Jmjd1c mRNA was expressed in fertilized egg, blastocyst, undifferentiated ES cells, embryonic germ cells, c-Kit+/Sca-1+/Lin- hematopoietic stem cells, pancreatic islet, and other tissues. Comparative genomics analyses revealed that binding sites for POU5F1 (OCT3/OCT4), AP-1, and bHLH transcription factors within the promoter region located 5' to exon 1B of human JMJD1C gene were conserved in chimpanzee, cow, mouse and rat JMJD1C orthologs. POU5F1-mediated expression of JMJD1C histone demethylase is implicated in the reactivation of silenced genes in undifferentiated ES cells, pancreatic islet, and diffuse-type gastric cancer.
基因组DNA和组蛋白的表观遗传修饰会改变染色质结构，从而调节转录因子与启动子或增强子区域的结合能力。2003年，我们鉴定并表征了JMJD1C（TRIP8），它由具有C2HC4型锌指样基序的TRI8H1结构域、具有甲状腺激素受体β结合区域的TRI8H2结构域和JmjC结构域组成。具有共同结构域架构的JMJD1A（TSGA）、JMJD1B（5qNCA）和JMJD1C是参与基于核激素受体的转录调控的组蛋白H3K9去甲基化酶。在此，报告了关于JMJD1C基因的比较整合组学研究。先前报道的JMJD1C变体1由外显子1、2和3 - 26组成，而本研究中表征的JMJD1C变体2是从位于外显子3上游的新外显子1B转录而来。4个人类JMJD1C ESTs是从外显子1转录的，而14个人类JMJD1C ESTs是从外显子1B转录的。26个小鼠Jmjd1c ESTs全部是从外显子1b转录的。这些事实表明，从外显子1B转录的JMJD1C变体2是主要转录本。具有TRI8H1、TRI8H2和JmjC结构域的人类JMJD1C变体2与小鼠Jmjd1c的总氨基酸同一性为85.7%。人类JMJD1C mRNA在未分化的胚胎干细胞、胰岛、弥漫型胃癌以及其他组织或肿瘤中表达。小鼠Jmjd1c mRNA在受精卵、囊胚、未分化的胚胎干细胞、胚胎生殖细胞、c-Kit+/Sca-1+/Lin-造血干细胞、胰岛以及其他组织中表达。比较基因组学分析表明，人类JMJD1C基因外显子1B上游启动子区域内POU5F1（OCT3/OCT4）、AP-1和bHLH转录因子的结合位点在黑猩猩、牛、小鼠和大鼠的JMJD1C直系同源基因中是保守的。POU5F1介导的JMJD组蛋白去甲基化酶的表达与未分化的胚胎干细胞、胰岛和弥漫型胃癌中沉默基因的重新激活有关。
