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Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation
Gao, Shan1; Xiong, Jie2,3; Zhang, Chunchao4; Berquist, Brian R.5; Yang, Rendong6; Zhao, Meng6; Molascon, Anthony J.1; Kwiatkowski, Shaina Y.1; Yuan, Dongxia2; Qin, Zhaohui6,7; Wen, Jianfan3; Kapler, Geoffrey M.5; Andrews, Philip C.4,8,9; Miao, Wei2; Liu, Yifan1; Miao, W (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China.
2013-08-01
Source PublicationGENES & DEVELOPMENT
ISSN0890-9369
Volume27Issue:15Pages:1662-1679
AbstractReplication of nuclear DNA occurs in the context of chromatin and is influenced by histone modifications. In the ciliate Tetrahymena thermophila, we identified TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA replication stress, manifested by the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions, including replication origins, as hot spots for replication stress in Delta TXR1 cells. Delta TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while Delta EZL2 cells, deleting a Drosophila E(z) homolog, were deficient in H3K27 di- and trimethylation, with no detectable replication stress. A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of Delta TXR1, corroborating H3K27me1 as a key player in DNA replication. Additionally, we demonstrated interactions between TXR1 and proliferating cell nuclear antigen (PCNA). These findings support a conserved pathway through which H3K27me1 facilitates replication elongation.; Replication of nuclear DNA occurs in the context of chromatin and is influenced by histone modifications. In the ciliate Tetrahymena thermophila, we identified TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA replication stress, manifested by the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions, including replication origins, as hot spots for replication stress in Delta TXR1 cells. Delta TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while Delta EZL2 cells, deleting a Drosophila E(z) homolog, were deficient in H3K27 di- and trimethylation, with no detectable replication stress. A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of Delta TXR1, corroborating H3K27me1 as a key player in DNA replication. Additionally, we demonstrated interactions between TXR1 and proliferating cell nuclear antigen (PCNA). These findings support a conserved pathway through which H3K27me1 facilitates replication elongation.
SubtypeArticle
KeywordHistone Methyltransferase H3 Lys 27 Methylation Replication Stress Replication Elongation Ssdna Replication Origin
Department[Gao, Shan ; Molascon, Anthony J. ; Kwiatkowski, Shaina Y. ; Liu, Yifan] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA ; [Xiong, Jie ; Yuan, Dongxia ; Miao, Wei] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China ; [Xiong, Jie ; Wen, Jianfan] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Wuhan 430072, Peoples R China ; [Zhang, Chunchao ; Andrews, Philip C.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA ; [Berquist, Brian R. ; Kapler, Geoffrey M.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA ; [Yang, Rendong ; Zhao, Meng ; Qin, Zhaohui] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA ; [Qin, Zhaohui] Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA ; [Andrews, Philip C.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA ; [Andrews, Philip C.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA
DOI10.1101/gad.218966.113
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant ; NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant ; NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant ; NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant
Indexed BySCI
Language英语
WOS Research AreaCell Biology ; Developmental Biology ; Genetics & Heredity
WOS SubjectCell Biology ; Developmental Biology ; Genetics & Heredity
WOS IDWOS:000322716000005
WOS KeywordRIBOSOMAL-RNA GENES ; EUKARYOTIC DNA-REPLICATION ; NUCLEAR ANTIGEN PCNA ; SINGLE-STRANDED-DNA ; S-PHASE CHECKPOINT ; CHROMATIN-STRUCTURE ; CELL-CYCLE ; HETEROCHROMATIN FORMATION ; GENOME STABILITY ; DAMAGE RESPONSE
Funding OrganizationNIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant ; NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant ; NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant ; NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19611
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorMiao, W (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China.
Affiliation1.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
2.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
3.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Wuhan 430072, Peoples R China
4.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
5.Texas A&M Hlth Sci Ctr, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA
6.Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA
7.Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA
8.Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
9.Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA
Recommended Citation
GB/T 7714
Gao, Shan,Xiong, Jie,Zhang, Chunchao,et al. Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation[J]. GENES & DEVELOPMENT,2013,27(15):1662-1679.
APA Gao, Shan.,Xiong, Jie.,Zhang, Chunchao.,Berquist, Brian R..,Yang, Rendong.,...&Miao, W .(2013).Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation.GENES & DEVELOPMENT,27(15),1662-1679.
MLA Gao, Shan,et al."Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation".GENES & DEVELOPMENT 27.15(2013):1662-1679.
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