downregulation of histone h3 lysine 9 methyltransferase g9a induces centrosome disruption and chromosome instability in cancer cellsg9a downregulation 9组蛋白h3赖氨酸的甲基转移酶诱发中心体中断并在肿瘤细胞染色体不稳定.pdfVIP

Downregulation of Histone H3 Lysine 9 Methyltransferase G9a Induces Centrosome Disruption and Chromosome Instability in Cancer Cells 1,2 2 2 2 1 Yutaka Kondo *, Lanlan Shen , Saira Ahmed , Yanis Boumber , Yoshitaka Sekido , Bassem R. Haddad3,4, Jean-Pierre J. Issa2 1 Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan, 2 Department of Leukemia, The University of Texas at M.D. Anderson Cancer Center, Houston, Texas, United States of America, 3 Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, D.C., United States of America, 4 Lombardi Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, D.C., United States of America Abstract Background: Modifications of the histone amino-terminal tails affect access of regulatory factors and complexes to chromatin and thereby influence biological processes. Cancer cells are characterized by prominent epigenetic dysregulation, including histone modifications. However, the functional roles of the histone methyltransferases (HMT) in cancer remain unclear. Methodology/Principal Findings: We studied RNAi-based inhibition (knockdown, KD) of 2 different H3K9 HMTs, SUV39H1 and G9a. Knockdown of the 2 HMTs in PC3 cancer cell line markedly inhibited cell growth and caused profound morphological changes with loss of telomerase activity and shortened telomeres. SUV39H1 KD cells showed substantial increase in G2/M fraction. G9a KD cells showed increased DNA content (1.7-fold in 2 independent clones) compared with FACS analyses to control. Karyotype analyses