Tropel Philippe, Jung Laura, André Cécile, Ndandougou Adeline, Viville Stéphane
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR1704, Université de Strasbourg , Illkirch, France .
Stem Cells Dev. 2017 Aug 1;26(15):1100-1110. doi: 10.1089/scd.2017.0057. Epub 2017 Jul 10.
Deubiquitinating enzymes may play a major regulatory role in pluripotent stem cells (PSCs), but few studies have investigated this topic. Within this family of enzymes, we found that the ubiquitin-specific peptidase USP44, is highly expressed in embryonic stem cells, induced PSCs (iPSCs), and testes as compared with differentiated progenies and somatic organs. Analysis by quantitative polymerase chain reaction and 5' RACE showed that alternate promoters are responsible for expression in PSCs and organs. We noticed seven regions of transcription initiation, some of them with cell- or tissue-specific activity. Close analysis showed that one of the promoters involved in stem cell- and testis-specific activity is differentially regulated in those tissues. At the epigenetic level, USP44 transcription was correlated with DNA methylation of a CpG island close to the main promoter region. These data imply a complex picture where regulating factors such as OCT4 may interact with other epigenetic mechanisms to regulate USP44 expression in PSCs and testes.
去泛素化酶可能在多能干细胞（PSC）中发挥主要调节作用，但很少有研究探讨这一主题。在这个酶家族中，我们发现泛素特异性肽酶USP44在胚胎干细胞、诱导多能干细胞（iPSC）和睾丸中高度表达，与分化后代和体细胞器官相比。通过定量聚合酶链反应和5'RACE分析表明，交替启动子负责PSC和器官中的表达。我们注意到七个转录起始区域，其中一些具有细胞或组织特异性活性。仔细分析表明，参与干细胞和睾丸特异性活性的启动子之一在这些组织中受到差异调节。在表观遗传水平上，USP44转录与靠近主要启动子区域的一个CpG岛的DNA甲基化相关。这些数据暗示了一个复杂的情况，即OCT4等调节因子可能与其他表观遗传机制相互作用，以调节PSC和睾丸中USP44的表达。
