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The lysine demethylase dKDM2 is non-essential for viability, but regulates circadian rhythms in Drosophila

Yani Zheng, Yongbo Xue, Xingjie Ren, Xiao-Jun Xie, Mengmeng Liu, Yu Jia, Xiao Li, Ye Niu, Jian-Quan Ni, Yong Zhang, Jun-Yuan Ji
doi: https://doi.org/10.1101/291070
Yani Zheng
*Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843
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Yongbo Xue
†Department of Biology, University of Nevada, Reno, Nevada 89557
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Xingjie Ren
‡Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing 100084, China
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Xiao-Jun Xie
*Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843
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Mengmeng Liu
*Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843
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Yu Jia
‡Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing 100084, China
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Xiao Li
*Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843
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Ye Niu
†Department of Biology, University of Nevada, Reno, Nevada 89557
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Jian-Quan Ni
‡Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing 100084, China
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  • For correspondence: nijq@mail.tsinghua.edu.cn yongzhang@unr.edu ji@medicine.tamhsc.edu
Yong Zhang
†Department of Biology, University of Nevada, Reno, Nevada 89557
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  • For correspondence: nijq@mail.tsinghua.edu.cn yongzhang@unr.edu ji@medicine.tamhsc.edu
Jun-Yuan Ji
*Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843
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  • For correspondence: nijq@mail.tsinghua.edu.cn yongzhang@unr.edu ji@medicine.tamhsc.edu
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Abstract

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 in the whole organisms 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 one hour shorter than the control. Interestingly, opposite defects 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 how dKDM2 and its orthologs in vertebrates regulate circadian rhythms will advance our understanding of the epigenetic regulations of circadian clocks.

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Posted March 28, 2018.
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The lysine demethylase dKDM2 is non-essential for viability, but regulates circadian rhythms in Drosophila
Yani Zheng, Yongbo Xue, Xingjie Ren, Xiao-Jun Xie, Mengmeng Liu, Yu Jia, Xiao Li, Ye Niu, Jian-Quan Ni, Yong Zhang, Jun-Yuan Ji
bioRxiv 291070; doi: https://doi.org/10.1101/291070
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The lysine demethylase dKDM2 is non-essential for viability, but regulates circadian rhythms in Drosophila
Yani Zheng, Yongbo Xue, Xingjie Ren, Xiao-Jun Xie, Mengmeng Liu, Yu Jia, Xiao Li, Ye Niu, Jian-Quan Ni, Yong Zhang, Jun-Yuan Ji
bioRxiv 291070; doi: https://doi.org/10.1101/291070

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