The Lysine Demethylase dKDM2 Is Non-essential for Viability, but Regulates Circadian Rhythms in Drosophila

Frontiers in Genetics

Xingjie Ren¹  Jun-Yuan Ji¹  Yani Zheng²  Xiao Li²  Ye Niu²  Yong Zhang³  Mengmeng Liu³  Yu Jia⁴  Jian-Quan Ni⁴  Yongbo Xue⁴ 

[1] Department of Biology, University of Nevada, Reno, Reno, NV, United States;;Department of Molecular and Cellular Medicine, College of Medicine, Texas A&Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing, China;M University Health Science Center, College Station, TX, United States;

关键词: KDM2;    demethylase;    development;    circadian rhythms;    Drosophila;   

DOI  :  10.3389/fgene.2018.00354

来源: DOAJ

【 摘 要 】

Post-translational modification of histones, such as histone methylation controlled by specific methyltransferases and demethylases, play critical roles in modulating chromatin dynamics and transcription in eukaryotes. Misregulation of histone methylation can lead to aberrant gene expression, thereby contributing to abnormal development and diseases such as cancer. As such, the mammalian lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either oncogenic or tumor suppressive depending on specific pathological contexts. However, the role of KDM2 proteins during development remains poorly understood. Unlike vertebrates, Drosophila has only one KDM2 homolog (dKDM2), but its functions in vivo remain elusive due to the complexities of the existing mutant alleles. To address this problem, we have generated two dKdm2 null alleles using the CRISPR/Cas9 technique. These dKdm2 homozygous mutants are fully viable and fertile, with no developmental defects observed under laboratory conditions. However, the dKdm2 null mutant adults display defects in circadian rhythms. Most of the dKdm2 mutants become arrhythmic under constant darkness, while the circadian period of the rhythmic mutant flies is approximately 1 h shorter than the control. Interestingly, lengthened circadian periods are observed when dKDM2 is overexpressed in circadian pacemaker neurons. Taken together, these results demonstrate that dKdm2 is not essential for viability; instead, dKDM2 protein plays important roles in regulating circadian rhythms in Drosophila. Further analyses of the molecular mechanisms of dKDM2 and its orthologs in vertebrates regarding the regulation of circadian rhythms will advance our understanding of the epigenetic regulations of circadian clocks.

【 授权许可】

Unknown