Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Institute for Biology, Freie Universität Berlin, 14195, Berlin, Germany.
Sci Rep. 2017 Jul 12;7(1):5240. doi: 10.1038/s41598-017-05004-w.
Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes. Generation of molecularly defined null mutants revealed that loss of 8 out of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent with their ascribed role in regulating chromatin organization. However, most JmjC genes do not critically regulate development, as 10 members are viable and fertile with no obvious developmental defects. Rather, we find that different JmjC mutants specifically alter the phenotypic outcomes in various sensitized genetic backgrounds. Our data demonstrate that, rather than controlling essential gene expression programs, Drosophila JmjC proteins generally act to "fine-tune" different biological processes.
Jumonji (JmjC) 结构域蛋白通过组蛋白去甲基化来影响基因表达和染色质组织，这为调节整个基因组中基因的活性提供了一种手段。JmjC 蛋白与许多人类疾病有关，包括各种癌症、发育和神经紊乱，然而，所有 JmjC 蛋白的共同生物学特性和对生物体发育和组织稳态的可能共同贡献尚不清楚。在这里，我们系统地测试了所有 13 个果蝇 JmjC 基因的功能。分子定义的缺失突变体的产生表明，13 个 JmjC 基因中的 8 个基因的缺失改变了位置效应斑（PEV）表型，这与它们在调节染色质组织中的作用一致。然而，大多数 JmjC 基因并不严格调控发育，因为 10 个成员具有生存能力和生育能力，没有明显的发育缺陷。相反，我们发现不同的 JmjC 突变体在各种敏感的遗传背景下会特异性地改变表型结果。我们的数据表明，果蝇 JmjC 蛋白不是控制必需的基因表达程序，而是通常作用于“微调”不同的生物学过程。
